Parkinson's Focus Today

Anxiety and Parkinson's Disease

2011-11-14T18:26:00.004-05:00

We Don't Know Why but Anxiety Is a PD symptom

Frankly, at this time, I'm not so concerned with the why but rather the effect of anxiety on Steve's Parkinson's disease progression. While anxiety is not unexpected when one receives a diagnosis, from what I've read, it is a more common symptom in PD than in say Diabetes, Rheumatoid Arthritis and Multiple Sclerosis. As a matter of fact it is a PD precursor symptom, often accompanied by pessimism. I always thought that Steve was over-thinking things and expressing them in a negative way; now I realize that this was a PD potential rearing its head when he was still a young man.

What we do know is that embarrassment is a risk factor for anxiety and social fears. We know that there might be an association with levodopa although probably not the other PD meds. We know that there may be an association with norepinephrine (dopamine is the norepinephrine precursor so you can't have one without the other) and we know that there are several other neural pathways which might contribute. We've got our eye on Serotonin and GABA.

Here's the thing, we know that anxiety was behind Steve's first bout of dehydration even though the underlying issue was actually Benign Prostatic Hyperplasia (BPH) or enlarged prostate. This in turn exacerbated feelings of urinary incontinence which in its own turn triggered extreme anxiety - enough to stop all fluid intake except for a morning cup of coffee and enough water to swallow pills and supplements. We focused on the dehydration, how to rehydrate and how to get him back on his feet to think and to function on his own again. We treated the cause and he started taking a common (and risky) prostate medication which he had turned down a several years earlier when he and his doctor discussed his prostate issue and actually checked for and ruled out prostate cancer. But we never looked at the other issue - the anxiety which overrode all else.

The treatments for PD anxiety at this time are problematic. Antidepressants of various classes: Tricyclics, SSRIs, Anti-psychotics, Benzodiazepines, and non-selective MAOIs. In early 2010 we just weren't ready to risk the motor symptom treatment for the anxiety/non-motor symptom.

So what happened in the late summer and early fall with the second round of dehydration? The second time around was easier to spot and know what to do. I was prepared already with electrolyte beverages - mostly fruit flavored. We kept the drinks flowing. He prefers ice water from the pitcher. We had the adult incontinence briefs on hand to relieve the issue of weakened ability to get to the bathroom on time and to get through the night. Although there was no question of doing the right things for recovery, each time there seems to be a larger cognitive deficit.

We recently made some other nutritional supplement changes and I adjusted up and down to determine if they constituted any part of the problem. All the time, the vivid dreams, the hallucinations and illusions increased making Steve's reality very confusing; contributing to the a high anxiety level.

We finally resorted to using an herbal to help with the anxiety after I realized that he was self-medicating with aspirin and found an empty bottle - which had been almost full a week before. I read everything I could find about the herbal components because it does help relieve the anxiety on a short term basis. The best I can say is that it seems to have the fewest contraindicated ingredients. Certainly a better option now than prescription medications.

In addition to retreating to the safety of his bedroom for frequent naps - mostly because he feels anxious, one significant new issue was freezing. We are still working through this problem. Steve now has his key words to help him through the tight spots but it took 3 months and he intermittently lets panic rule so that he mixes up the words in the commands: Look Up and Walk Forward. Mostly they had a calming effect and then anxiety takes over and the words become other words - the wrong commands.

I can now see that fear in his shuffle step. It makes me wonder how many shufflers out there are just plain scared. I hadn't seen it in those movements for many months but now I recognize the enemy. It isn't just postural instability - a precursor or early symptom of his - it is his terror that something bad will happen on the next step.

I know he has recovered just enough arm swing with the new form of buffered creatine monohydrate that he can walk at a slow pace but with a normal balanced stride, shifting his weight from side to side, using his shoulders to propel himself forward (that's Walk Forward) He has to be reminded in the early morning, when he wakes from a nap and in the evening but sometimes he can let himself relax enough to walk without anxiety. That makes my heart sing.

Watch those stairs

Our next project will be stairs. He's gone downstairs only a few times since the dehydration but he had few problems going down and none on the way back up. But he is afraid. He sees a black hole and not the steps leading to the 1st floor. He is anxious every time he walks past the stairway. His sister, a nurse, mentioned that perhaps it is eyesight issues which help trigger the fear and we'll check that possibility.

We're looking for solutions to the anxiety, the cognition losses, and the PD psychosis which play a large part in making his world a more frightening place. One possible solution may lie in a clinical trial taking place in our neck of the woods. We provided a link to the Fox Trial Finder in the right column under Clinical Trials but how serendipitous to have a reminder email from PAN (Parkinson's Action Network) this morning. I used that link, and looked at trials in our area again and found some new ones. So we sent an email to the Pimavanserin Trial, heard back promptly with a phone number and are waiting to hear back from the Cleveland Clinic Study Coordinator. We are hoping that if the psychosis can be treated, we can work more effectively to lessen the anxiety.

Additional Reading:
Anxiety disorders in Parkinson's disease: prevalence and risk factors

Anxiety Affliction in patients with Parkinson's disease
Parkinson's disease: depression, personality and anxiety
Pessimism and Anxiety Linked to Parkinson's

The Effects of Added Stress in Parkinson's Disease

2011-08-05T17:50:00.005-04:00

Does Stress Exacerbate PD Symptoms?
Dehydration Brought on by Stress

Things have been a bit hectic around here for the last several weeks. Hectic means that Steve will be become stressed no matter how things are handled. And stress means that there is little predictability about how he will react. Here it meant that Steve was growing steadily more anxious about the impending appearance of the roofing crew. Strangers were going to be all over his roof doing work which he could no longer supervise let alone climb the ladders to monitor. To top it off family dogs were spending their parents' vacation with us.

Having a father-daughter chat

The Corgis didn't come to Ohio this summer to brighten the days with their grins and antics but our daughter was able to spend some quality time with Steve. After Lois left for Georgia, the English Setters arrived while their mom and dad traveled to New England to repair plumbing and visit aging AD parents .

For me the roofing job was stressful in terms of $$$$$ spent and the not-so-hot clean-up which followed but it was a relief to have the roof leak-free. It should outlast us. For Steve it was the stress of unknown people, sun-up to sunset noise, and chaos that sent him around the corner to a darker place.

We know that stress means that the PD patient will become more symptomatic. Tremors appear more frequently. If Steve is severely stressed, his entire body might shake. As soon as he calms down, that shaking will stop as abruptly as it began. But it is the psychological symptoms which really affect his physical state. When feeling stressed, one symptom is that he manifests is feeling that he has to urinate more often - not unusual - but in the case of many men, it means that he is going to lower his fluid intake to avoid accidents. His body also becomes more rigid and he walks with a tiny shuffle severely impacting his balance.

In this hot summer with fans but no central air conditioning, the sweat level has also been high. And that feeling of heat fatigue is not conducive to drinking more water to compensate but rather to begin the shut down. Dehydration looks a lot like the end stages of Parkinson's.

Although I caught the dehydration symptoms early and tried to monitor the water consumption, he pulled a water bottle bait and switch on me and it was a few days before I realized that he was showing me the older empty bottles. And then...the bottom fell out.

Let's face it, caregivers are often pushed to their limits by their charges. Whether you are a spouse, sibling or child, there comes a time when the fear and the urgency of the situation (feels as if it) forces us from gentle into harpy mode. He complains that he is dying and you find yourself in the body of a screaming bitch who is yelling, Do you want to live? Then stop trying to kill yourself. Help me help you! There is no question that the fear-factor forced him to give this some thought by the next morning and he was more open to suggestion but still quite demanding..

Even though Steve never cared about really cold drinks, ice water has helped more than anything else. It isn't a lot of ice water at one time but rather, smaller amounts frequently...we topped off everything with a few sips through the straw. (Yes, I know he doesn't like straws but they are helping) I mixed his creatine (which must be first dissolved in very warm water) with ice cold blueberry/pomegranate juice. And he now downs it promptly. We use 2 or 3 trays of ice cubes a day just on his ice water. Too much water can also be damaging to the system - more is not always better just as less is always not more.

Instead of going through weeks and weeks of a debilitating condition as he did in the winter of 2009-2010, he is coming back steadily from that horrible place. He can walk down the hall without help; although the cane is useful with four dogs around. He can get into bed on his own again. Am I going to let him select his medications and supplements from the organizer? Not for awhile yet - perhaps not again.

Eventually we will report on adult underwear and other incontinence aids we have used. Some are clearly more absorbent than others. For now, the fever is gone, the total confusion is ending, he is neither helpless nor totally rigid in the morning, unable to get out of bed. Yes, he needs encouragement to gently stretch before sitting up. At least now he can do that.

He has been miserable as he saw everything seem to vanish over night. Cognition, movement, bladder control, ability to dress, to function. He couldn't even use the TV remote a few days ago; now he's back to switching programs I am listening to in midstream. He walks down the hall easily pushing aside the rawhide dog chews and gently tapping with his care to ask a resting canine to move clear of his path. He has even become more careful with his special PD prisim lenses because he is back online and can't see the monitor without these glasses.

Topper watching roofers
Willson sleeps comfortably

Despite Steve's fussing, I firmly believe having the Setters visit was a help for both of us, not to mention Harry and Rita. The silky Setters make for delightful and calming petting in the temporary absence of the cats. While Blakey comes upstairs to complain from time to time, he has chosen to spend most of his time in the much cooler dehumidified basement with Mongo who does not like any dogs but his own.

Next year we may add a dehumidifier for the 2nd floor. And next week I'll lay in a better supply of drinks to compensate for electrolyte loss. We're going to add cocomut water and Gatorade to the pantry.

Parkinson's Disease Clinical Trial Finder Customized for You

2011-06-24T15:14:00.012-04:00

You can now register for the Fox Trial Finder for PD Clinical Trials
Follow the link at the bottom of this post

As you have probably surmised, we are believers in clinical trials. For some they are a way to contribute to the body of knowledge, for others they are a way to gain early access to potential treatments which might work for them. Early access generally means that the treatment will be available at no cost until it is marketed.

The Michael J Fox Foundation has created a new way to find a Parkinson's disease clinical trial suited for your personal needs in a location close to your residence. You have the option to select the distance from your home and to change it later if you cannot find trials within the initial range.

Although the Fox Trial Finder won't be up and running for a couple of weeks, it is not too soon to register to receive notification. We've already registered; you can too.

Entering your information into the Trial Finder itself can take a few minutes. You complete by checking the boxes on the form, save the info and move on to the questions on the next page. By doing this you can make sure that you are not wasting your time later or getting your hopes up for a trial which is too far away or for which you cannot participate. You can always reset the distance from your home or make other adjustments in the search parameters as there are changes in your life or lifestyle.

For those of us who have used Clinical Trials.gov, the initial input - the search parameters - are brief but you still have to do considerable reading to find a trial that is specific to your needs. Although you will still have to review the exclusionary info, you will have a personally directed search.

We've been fortunate enough to be able to preview the Fox Trial Finder and think it will benefit those in search of trials because of their specific PD issues. We'll post a direct link in July when it is up and running.
July 14, 2011
Check out the new Fox Trial Finder: Click here for a direct link to the Fox Trial Finder
According to MJFF: With Fox Trial Finder, you can create a profile including basic information about yourself (such as location and experience with PD) to identify your potential clinical trial matches. Registered users have the ability to review trial matches, bookmark interest in trials, and send messages directly – and anonymously – to trial coordinators registered on Fox Trial Finder.

Don't forget to adjust the mileage bar in the left column to the farthest distance you are willing to travel for a trial - if you don't, you'll receive results from the next state or more.
You can also see the subjects of the trials in the left margin and can simply select a topic.

Random Thoughts and Ideas about Parkinson's Disease

2011-06-17T14:00:00.076-04:00

PD is always with us even when we ignore it

An apology is in order for the dearth of posts lately. We've been tweaking past posts and side column information and now we'd like to share some random thoughts we've had recently.

Lifestyle aids - If you look hard enough you'll find several interesting products including scissors. At one point in our household there were two lefties. One had to have a lefty scissors, the other couldn't use one. But this is different. There is a long reach scissors for helping with toenails. We don't know if it is really long enough but it might help. There is also a table top mounted scissors which might help for those who can only use one hand.

We wrote about other basic assistive devices a few years ago. It's always a good idea to keep checking because people are always finding clever ways to help adapt to PD issues. We would appreciate your input on experience with adult incontinence underwear brands through your comments below or by email.

Toe Cramps? If a calcium/magnesium along with a potassium supplement doesn't work, perhaps Gel Flex Toe Stretchers or YogaPro Yoga Toes might help. They look sort of like the foam pads I tried to use for separating my toes to keep nail polish from smearing. Would those work too? Those will cost about $2.00 for a pair.

The laser mobility walker for Parkinson's disease. Made by U-step who also makes a laser cane, these walkers are not inexpensive although you can still get considerable support form Medicare for their purchase. This is a heavy duty walker with seat and basket, the laser device which helps to break a freeze can be purchased separately.

We've only mentioned medical alert tags once, but the more we read anecdotal experiences, the more we realize just how important these dog tags, pendants, wallet cards, bracelets can be. It is important that the information be on the tag itself. There are several companies which can create this identification for you. Consider how symptomatic you might become or how painful withdrawal might be if medical personnel did not have your medication information upon admission to the hospital...or even before that.

Multi-tasking. In ADHD low levels of dopamine prevent a child from focusing - is that similar to the lowered ability of PwPs to multi-task?

Saw this little guy down the street
We were delighted to see him
No imagination required

Hallucinations vs imagination How do we distinguish between seeing faces and animals in the cloud shapes and hallucinating that we are Seeing Faces in clouds, carpets and patterns when dopamine levels are elevated? "Life isn't about waiting for the storm to pass. It's about learning to dance in the rain." "Will you, won't you, will you, won't you, will you join the dance?" And if not the dance, will you walk or march with me?

Walking and arm swing - did you know that it takes more energy to walk with your arms still than to swing them? Arm swing helps to counterbalance the body - keeping your hips from twisting too much. It has been learned that if you walk with the leading leg and the arm swing on the same side of the body (think Pacer in horse racing) it actually requires 25% more energy than a normal walk with leading leg and opposing arm swing. So where is it in the brain? As evidenced by DBS surgery and possibly PD levodopa treatment, upper arm locomotor synergies are influenced by the basal ganglia.

Steve has been taking a different form of Creatine for the last few weeks and has regained a small amount of arm swing on that PD side. Although we switch brands of supplements from time to time, we're going to be sticking with CreaSol, a flavored powder which is mixed with warm water.

Ayruvedic medicine promotes walking as an activity which will bring the various energies of the body into balance. Walking is low impact and considered to be a healthy activity for all body types. We're glad to report that Steve has started taking walks again. This means that he has been reporting back on the garage sales and who is setting up a wedding tent in the back yard. Walking can be very valuable.

We know that the rhythm of the dance apparently helps people with PD move in ways their condition suggests they can no longer move. How do You walk to music? We know that music is an anxiotic -an anti-anxiety aid. We know that music can actually have analgesic properties. It can decrease heart rate, respiration rate, and blood pressure. Music has been used for therapy since early times. Rhythm is just one aspect which seems to be very helpful in PD. If you don't want to get out of that chair, listen to the music.

So what about melatonin, the nighttime hormone produced by the pineal gland? Is it just another push-me-pull-you of PD? Exposure to sunlight suppresses melatonin production. Melatonin release then inhibits the release of dopamine in specific areas of the central nervous system (hypothalamus, hippocampus, medulla-pons, and retina). It is possible that this in turn plays a role in the causation of PD since inhibition of dopamine will have consequences on bodily movements. Although the antioxidant effect of melatonin may offer neuroprotection for mitochondrial activity, the inhibition of dopamine release is not a goal of PwPs.

CoQ10 and Parkinson's disease. Ok, CoQ10 trials have come to a halt. Co-enzyme Quercetin 10 does not slow the progression of PD. Steve found that it definitely made him feel better in the early years of his PD. He found that it did help with tremor easing. Did he think it was slowing progression? He felt that it was helping with symptomatic relief. And that in itself is significant. We need larger studies in the improvement of PD visual function because another small study had positive results. Moreover, two studies for cardiac patients had positive results. In one CFS study, patients who took CoQ10 demonstrated a serious reduction in congestive heart failure symptoms and had required fewer hospitalizations. One heart transplant patient study had only minimally positive results while a shorter, smaller study had some positive results.

Steve and Rita on a walk in the park

Rhinorrhea or Rhinitis is increased in PD. Who would think that a runny nose would be symptomatic of PD but according to Dr Joseph H Friedman, that is exactly the case. They have not determined whether it is related to olfactory deficits as well but it is not only a symptoms but it can be a precursor symptom as well. I've noticed the increased need for throat clearing due to post nasal drip with Steve. Once he's done that, it is much easier to understand him when he speaks. Rhinorrhea in Parkinson's disease by Dr Joseph H Friedman, MD Rhinorrhea: a common nondopaminergic feature of Parkinson's disease.

Seborrhoeic dermatitis - autonomic symptom - immunodeficiency - aloe vera or coconut oil - crude diluted honey - avocado extracts and supplements such as lactobacillus, B vitamins: B7 (biotin), B6, B2, B3. Alternative treatment= apply milk of magnesia to face or scalp when showering (rinse off at end of shower)

Autonomic Neuropathy a form of peripheral neuropathy, is found in symptoms which occur when there is damage to the nerves which regulate blood pressure, heart rate, bowel and bladder emptying, digestion and impotence. So that helps to explain the Pd symptoms: constipation, urinary incontinence, urinary hesitancy, incomplete emptying of bladder and yes, RLS. It also helps to explain postural instability or dizziness upon standing or sitting up, hyperhidrosis (excessive sweating, difficulty swallowing.

In Parkinson's disease concerns are very real. Falling, weight loss leading to malnutrition, dehydration and electrolyte imbalance, choking. although rarely mentioned there is also a risk of kidney failure caused by urine back up accompanying incomplete emptying of bladder.

Which leads us to the symptoms of kidney problems which can lead to kidney failure if untreated. Headaches, aches and pains. Feeling tired all of the time. Loss of appetite. Bone and joint issues, itching and restless leg feeling. One problem is that a lower backache can be the only symptom and is associated more with stiffening muscles that with a kidney infection. It might be ignored. Anemia can develop because the red blood cell count is low. Low red blood cell count = low oxygen levels for cells. Insomnia/daytime sleepiness. The basic problem is that UTIs are common in latter stages of PD when organs begin to shut down and when catheters have become necessary. It is important for caregivers to be on the lookout for the signs.

Exercise aids - we've talked about the portable assisted pedaler in a previous post. We'll add the findings of other PD users as the reports come in.

On 9-18-11 we were sent a link for a pocket sized breathing exerciser:

Respiratory Muscle Strength Trainer, a simple hand-held device looking very much like a large whistle. Regular use should help improve the strength of the muscles used to inhale and exhale. Most everyone remembers having a whistle as a child. This devise might appeal to the aging but young at heart and demonstrate important therapeutic results.

Early Warning Signs of Parkinson's Disease

2011-04-02T20:30:00.017-04:00

Precursor Symptoms of PD - What's the Tipoff? And What Were Your Earliest PD Symptoms?

In retrospect; in hindsight; if only I'd known; I wish I'd looked for more answers; why didn't the doctor say something? I should have...done something more...

If the precursor symptoms are recognized as Parkinson's disease, can early intervention at least delay the onset?

Earliest warning symptoms of Parkinson's usually go ignored or are attributed to some other condition. There isn't a single symptom you or your loved one can have that is unique to PD, although as a group some are more unique. There are diagnostics which can rule out some many differential diagnoses even at this early date.

The biggest impediment to addressing the developing Parkinson's disease after the early warning signs or precursor symptoms appear is that we do not recognize them for what they are. We don't even know what they are.

Leg drag
Lack of Arm Swing
Loss of Sense of Smell - decreased sense of smell - phantom smells
Changes in Handwriting
Changes in Voice
Change in Facial Expression
Pain or achiness in the Shoulder or Neck, more common in women
Depression, anxiety, stress
Sleep problems - especially with especially with REM sleep or more specifically RBD sleep. Sleep issues may also include "acting out" during sleep: Yelling, kicking, punching.
Signs of specific Vitamin Deficiencies: Ds and Bs especially
Sharp small pains - pinprick pains - or perhaps small areas of numbness
An odd type of vertigo - which may actually be Orthostatic Hypotension which is known to develop years before the actual PD diagnosis
Dizziness
Adding additional symptoms beginning 4-05-11 with THANKS to the folks at Patients Like Me
Urinary issues such as urinary incontinence or frequency
Impairment of color discrimination - may improve with levodopa
Fatigue - tiring more easily at routine tasks - lack of stamina - daytime sleepiness
Cramping
Rhinorrhea - that's a runny nose to most of us
Seborrhoeic dermatitis - an autononic symptom, an immunodeficiency - flaking is often confused with dry skin - possibly seen as dandruff
numbness - usually in extremities
We would like to learn if people experienced any of the following as precursor - earliest - symptoms
Sleep apnea ?
Constipation
RLS - restless leg syndrome?
Excessive sweating - an autonomic nervous system dysfunction?
Personality changes or changes in Executive functioning
Hyperhydrosis or excessive sweating which can sometimes appear as Seborrhoeic dermatitis - might feel like hot flashes
Erectile Dysfunction
Vision issues such as dificulty focusing

In an era when there is access to symptoms of every conceivable disease at our fingertips, there is little information about PD precursor symptoms on the Internet. If you do a web search, you won't find much about them. I just did that and mostly what I found were articles I'd already written.

Think back to the months and even years before your diagnosis, what do you recall of the precursor symptoms? We're talking about those symptoms which you attributed to being tired, to stress or anxiety, to physical exertion, to anything but PD because that wasn't even a consideration.

So you are X-rayed, MRI'd, you have endocrine tests, thyroid tests, blood tests and a few more for good measure and that's good because it makes sense with these early symptoms. But PD doesn't show up on these kinds of tests currently. And then what happens?

The doctor rules out a condition or two and then gives you the verdict: "Well, you don't have X*X?." And that's it. You pay your bill, you go home, your spouse asks what the doctor said and you say, "Well I don't have X*X?." Many of us have been trained to accept this kind of negative diagnosis, but that's wrong. We can all do better.

As families and patients we have a right to expect some positive action. And doctors should certainly know this. That message needs to be sent from the patient base if it isn't taught in medical schools. As patients we have a responsibility too. We have to overcome the relief that we don't have X*X? and the fear of what comes next and we have to ask, "What comes next?"

The very early warning signs are now being recognized as an significant area of study but the symptom list is not ready for prime time yet. The communication from the research front will be forthcoming when the studies have been completed. The good news is that studies are now underway.

These studies represent a way in which people with PD can contribute. Even if we can't improve the future for ourselves, we can use what we have learned to improve the precious future of someone else, perhaps our children or grandchildren.

Listed at Clinical Trials.gov are three studies of especial interest:

Investigate neurophysiologic tests that have the potential of serving as screening tools- New Haven, CT
Consortium On Risk for Early-onset Parkinson's Disease (CORE PD) It is still recruiting at Columbia University, NY, NY and at Rush University Medical Center, Chicago, IL
Developing hindsight: Biomarkers of Risk of Parkinson Disease

Another source of information is found in the notes in patient files tucked away in doctors' offices. This is the information that needs to be shared at seminars, in articles. There would be no HIPAA violation, names would not be named but the symptoms could be compiled. Yes, it is a huge undertaking but it would make a remarkably useful study.

Our best body of knowledge now comes from proactive patients who share their stories. Not all are sucess stories but they demonstrate the importance of a the current studies and the importance of a productive doctor-patient relationship.

It is far more important for both the medical profession and the general public to raise their awareness of early warning symptoms of neurodegenerative diseases, especially Parkinson’s disease, because treatment can begin earlier. Now that there are more treatment and therapy options, it makes sense to try to slow onset.

What we are wondering is whether the immediate treatments will lie more in Alternative Medicine in the form of Nutritional Supplements rather than in pharmacological medications. What will be the role of therapies such as Forced Exercise?

Previous posts on subject:

Differential Diagnosis and Parkinson's disease

Questions about Parkinson's Disease

You might also be willing to contribute to the knowledge base by registering to participate in an NIH study:

Study Link for Biomarkers of Risk of Parkinson's Disease at the National Institutes of Health.

Check our this discussion of the Top Ten non-motor symptoms of Parkinson's disease from Dopadoc.

Cogane Clinical Trials Phase II for Parkinson's Disease

2011-03-31T17:22:00.001-04:00

The long awaited Cogane trial is recruiting

Is there a rainbow over the PD road?

If you are between 35 to 75 years of age and have a confirmed early-stage idiopathic Parkinson's disease within the last two years and are not receiving any PD treatment, you may be eligible for NCT01060878. Women of child-bearing potential are excluded although the study is open to both genders. The other exclusionary conditions are prior neurosurgical PD procedures and history or severe psychiatric illness.

The investigation into the efficacy, safety and tolerability of Cogane has now reached the phase II stage of clinical testing. This trial will be a double-blind, placebo-controlled study. We are not sure if it will be followed by an open label trial - wouldn't that be terrific if this GDNF approach is actually effective.

NCT01060878 is sponsored by Phytopharm. The investigation of Cogane (PYM50028) in Early-stage PD is now recruiting at the following locations:

In the United States
La Jolla, Sacremento and Sunnyvale, California

Manchester and New Haven, Connecticut

Chicago and Sprinfield, Illinois

St Louis, Missouri

Manhasset, NY

In Canada:

London, Ontario

Ottawa, Ontario
Quebec City, Quebec

In the United Kingdom
Luton, Bedfordshire
Newcastle upon Tyne, Tyne and Wear

additional reading:

Cogane, a Future Treatment with Hope for a PD Cure

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

There is additional ongoing research: The administration of BDNF and GDNF to the brain via PLGA microparticles patterned within a degradable PEG-based hydrogel: Protein distribution and the glial response

Call on Congress to Advocate for Parkinson's Disease

2011-03-01T04:09:00.007-05:00

Take a few minutes to support PD

It isn't often that we have an opportunity to do something important to help the Parkinson's disease cause. We know that people want to contribute. Now there is an opportunity for you, your friends and family to add your voice in grassroots support of to Call on Congress.

On Wednesday, March 2, 2011 a few hundred advocates will be personally meeting with Senators and Members of House of Representatives to ask that they join the Congressional Caucus on Parkinson's disease, to Co-sponsor the National Neurological Diseases Surveilance System Act and to support biomedical research as well as therapy development at the National Institutes of Health.

While Parkinson's disease may discriminate about whom to attack, PD knows no political party boundaries. Call on Congress is more than a way to add your voice to the rest of the Parkinson's disease community while approximately 250 PD advocates have personal meetings with members of Congress and their staff members to advocate for awareness of the disease and the significant issues about PD. Call on Congress lets your legislators know that there are many PD constituents out there.

All it takes is a simple statement to your Congressman/woman begins with a single phone call or email in support of the passage of the revised National MS and Parkinnson's Disease Registries Act (HR 1362 and S 1273) now known as the National Neurological Diseases Surveillance System Act of 2011-2012 S.425. It will be introduced by Co-sponsor Senator Mark Udall, son of the late Morris Udall. As a matter of fact, PAN has already written the statement which you can edit to personalize or send as is.

USA coast to coast

One purpose of the bill is establish a national data surveillance system which can track and collect data on the epidemiology, incidence, prevalence, and other factors of neurological diseases, including Parkinson’s and MS. A primary goal is to be able to collect information from many sources in order to measure the incidence and prevalence of the disease. The implications of having accurate data and geographical information open doors to problem solving.

This afternoon we "attended" the Parkinson's Action Network webcast, Research Public Policy Forum. where the importance of Your/Our PD stories carries great weight not only with legislators but also the public. For the last several years we have begun to see the humanizing of a disease which for so many years was seen as a stereotype. We share our patient and caregiver back-stories with each other and now it is time to share a few lines with people who have the power to represent us.

Please remember to thank your legislator if you see your State represented.

Update: As you know, the National Neurological Diseases Surveilance System Act of 2011-2012 S.425.IS was introduced by Senator Udall. That does not mean it is a done deal. Continued public support is necessary. Follow the bill so that you can send the necessary reminders to your government officials.

"The bill will create, for the first time, separate, permanent, and coordinated MS and Parkinson's disease national registries at the Centers for Disease Control and Prevention (CDC). The registries will rely upon existing databases including Medicare, Veterans Affairs, state registries, and other databases to determine the incidence and prevalence of MS and Parkinson's disease across America."

It's Hard to Sleep with Parkinson's Disease

2011-02-07T15:24:00.003-05:00

More on Sleeping Problems and PD

Steve's sleep problem has reared its nasty head again.

Some sleep and some can't

As some readers know, Steve began a very low-gluten diet almost 1.5 years ago. He does not have Celiac's nor IBS but for some reason, it seemed worth a try. The result was that he found an improvement of his sleeping problems. Occasionally we will cheat or slip and a little too much gluten will find its way to his plate or glass with the resultant sleep disruption. That happened this week on a little status check.

The good news is that he says that gluten-free pumpkin pie tastes like a regular pie and I will respond that it is a regular pie with slight variations.

Steve did not have many sleep interruption issues prior to being diagnosed with PD, at least none that he would discuss or acknowledge. I do know that he would occasionally have very vivid dreams, some REM behavior, and some sinus breathing issues which he would ignore. In retrospect, the first two were alarms. What I do know is that he would fall asleep long before me and sleep through the night, oblivious to children or animals.

On a hot day, the only option

Another thing that we saw again this winter was a slip back into dehydration. Whew! We caught it before there was a serious progression and are addressing the problem in both Steve and Harry the dog. With Harry, starting him on chicken broth will usually do it; so I'm doing that again. He also likes to take a chomp from a snow pile on his way back into the house which suggests that he might prefer really cold water in his water bowl.

This morning I was trying to recall whether any other family four-foots had suffered similar issues. And there it was the seasonal changes which can cause horses to upset their electrolyte balance by not drinking. Griffin, our daughter's appendix registered Thoroughbred-Quarter Horse had the problem one fall. It’s pretty easy to see a pinch of skin that doesn't retract very rapidly. What to do? You can lead a horse to...but you can't...We had to go the electrolyte route. Sprinkled over feed and in a tubed paste - it worked; and he started sucking up water again.

That beer for the Super Bowl XLV was not a good idea; it could have upset all sleep for Steve last night. Not only was there gluten, there was alcohol which is dehydrating. He was smart enough to take a gulp or two and then set it down for the evening. I should have read the lists first - what wasn't I thinking?. The information abounds for gluten-safe alcoholic beverages.

Because the sleep issues are a PD symptom, they will not vanish. Because they can be exacerbated by dopaminergic treatment, they are not going away. The most common are the levodopas (Sinemet) and ropinerole (Requip).

We often forget the association between depression and sleep problems; how do you treat your depression?

A helpful catnap

Steve still has some prejudice against the afternoon nap, he feels he must resiste what he sees as excessive daytime sleepiness which he often feels after taking Sinemet. Nonetheless, he knows enough to take that nap.

Occasionally he will take an aspirin before bedtime. As a NSAID, it can't hurt and for some reason - perhaps pain relief - it helps him fall asleep. We also time the Vitamin B complex to just before bedtime. If he will drink plenty of fluids (water) during the day, he can ease of in the evening. If not, I am more concerned about the dehydration than his sleep - heartless creature that I am.

The best thing that he has done is to drink a cup of unsweetened chamomile tea with a little milk. He has found that to be sufficiently relaxing to help him go to sleep.

We've read that more than 80% of PwPs have sleep disorders or sleep dysfunction ranging from insomnia, excessive daytime sleepiness, and the parasomnias which include: sleep talking and walking, REM behavior disorders, sleep terrors. We have read about sleep apnea issues which should also be considered. There are CPAP (continuous positive air pressure) machines which can help. We;ve read and tried memory foam mattresses and Steve's favorite, the heated mattress pad, which is more effective for him than a heated blanket.

Oh for a Cat Nap

I'm over-the-top about some things but in treatment, I prefer the less is more approach to start. I'd like him to try breathing exercises again to help him relax before bedtime but since he is no linger having swallowing problems, he bristles at the words exercise and sleep in the same sentence. Still, I think they might help to release the tension and frustrations of the day. I cannot stress enough the importance of healthy breathing habits.

We are interested in hearing from others about what works for them...even the medications that work. We are also interested in hearing about things that worked for awhile even if they stopped working.

additional reading:

A must read by Dr Robert A Hauser etal

Parkinson's Updates, Odds, Ends, Beginnings

2011-01-31T00:50:00.012-05:00

PD Community Info Including Neupro Updates

If you missed the PD Expert Briefing on Physical Therapy and Parkinson's, What You Need to Know, you may have a second chance to watch, listen and to ask questions. Heather J Cianci, PT, Geriatric Clinical specialist, MS, trained in Lee Silverman Voice Therapy will be presenting the program again following a technical glitch.

We did attend the first broadcast - minus the slides - and although there wasn't a lot that we haven't written about on this blog, we still learned a few things. Parkinson's Disease Foundation (PDF) has announced that the rebroadcast will take place on Tuesday, February 8, 2011 at 1:00 EST

We have questions about the use of Low Dose Naltrexone (LDN) by people with Parkinson's and are hoping that people who who have or are currently using LDN will provide some feedback about the experiences. There is an LDN Worldwide DataBase that would also like to have your input. There is quite a bit of information submitted by Multiple Sclerosis (MS) patients, but very little on PD. Just select Parkinson's from the left hand buttons. We have also posted links in the LDN articles.

Currently there is a study funded by a grant from the Michael J Fox Foundation, NCT01052831 Dr David Weintraub of the University of Pennsylvania in Philadelphia is studying the safety and use of LDN for impulse control disorders in PD. This study is still enrolling and Dr Weintraub reports that there is some limited travel money available.

Because LDN already has FDA approval for one use, it is not economically feasible for a pharmaceutical company to fund one for the use of LDN and Parkinson's disease. For this reason much of the information is going to be anecdotal. That is why adding honest information at a website or database is important. To add a comment at this website, there is always the option to remain anonymous.

We’ve also read the responses to LDN discussion at Patients Like Me and we are encouraged enough to make this a priority for the next neurology appointment.

We just came across LDN Science and think you might want to check this site for LDN information.

There is hope for getting Neupro now

I'm sorry for the delay update about the Neupro (rotigotine) Transdermal Patch. I am pleased to report that although there is no program called "compassionate use" for people who were already using the patch prior to the withdrawal from the market and who have not been able to locate suppliers in other countries, there is an opportunity for people who have been on the patch and potential new users to receive it through the Named Patient Program, clinical trial.

We are providing a link to NCT0195484 which is a Named Patient Program with Rotigotine Transdermal System by invitation only study. The locations for the study are in Alabama, Arizona, California, Washington DC, Florida, Georgia, Hawaii, Illinois, Michigan, New Jersey, New York, North Carolina, Oregon, Texas and Washington.

We now have the contact email address and phone numbers so that your doctor can contact UCB to be sent the request for study enrollment form. The form would then be completed and mailed or faxed to UCB for consideration. A patient must be under a doctor's care for consideration. I suggest speaking with your prescribing doctor. We will be provide you with all of the contact info (email, phone, fax) at UCB by email if needed. Just click the email link.

OMG! We just found another Neupro Clinical Trial for PwPs in the USA who wanted to start the Neupro (rotigotine) Transdermal Patch only to find that it had been withdrawn from the market. There are strict inclusion and exclusion criteria but if the patient meets these, there is a possibility that you will be provided with the real patch. We don't know if there is an open label trial at the end or not but we will try to learn more. The trial is NCT00522379 and is of course sponsored by UCB, Inc. Check it out if you or a family member might benefit from this Neupro clinical trial.

Time may be running out to contribute to the funding supporting the making of Ride with Larry, a documentary about the cross-state ride of a retired police captain in South Dakota who bikes to work every day despite or perhaps because he has had Parkinson’s disease for about 20 years. Although they've made their goal, they can still use your help. You can see a trailer of the documentary and donate at the site below.

Laughter is good medicine

Paypal donations for the documentary can still be made at the documentary.org website. Just click the Make a Donation box. This is a 501(c)(3) organization.

People often ask what is the best medicine for Parkinson's disease and I must say that there is no best answer, what is best is what works to relieve your symptoms and will allow you to have the best quality of life possible. For most people, one medication, one treatment is not going to be enough. We still encourage everyone explore dietary adjustments; nutritional supplements of good quality; physical (exercise), speech, massage, occupational, music and dance therapy. Never forget the power of true laughter to feel better.

The Elephant in the PD Lab

2011-01-11T21:06:00.005-05:00

We need a better roadmap for Parkinson's Disease

The PD summit has yet to be conquered

People with Parkinson's can feel overwhelmed by the search for the most effective treatments and therapies. There are so many information bytes out there. You read all day, maybe purchase some full scientific articles only to find you don't actually understand enough or you see that the focus is so small that only scientists can analyze it. Without a photographic memory to categorize input, without huge resources how do you find your direction through the maze?

You wonder if you are the only one missing the keys? How do you take this mass of information and reduce it, refine it to create a map to actually get to a treatment which will not only stop progression but reverse it?

We have Centers of Excellence for research and treatment. The Morris K Udall Parkinson's Disease Research Act of 1997 was established in part "to provide for the expansion and coordination of research regarding Parkinson's disease, and to improve care and assistance for afflicted individuals and their family caregivers." But much of the research being done for PD and other conditions does not fall under that umbrella.

We have Clinical Guidelines for diagnosis and management of PD - primary and secondary care at the National Guidelines Clearinghouse.gov. The concept is both reassuring and frightening because it has an inherent structure which can slow progress of care but may not allow for slowing the progression of the disease without a readjustment period.

Searching for....

Every day we search through abstracts about Parkinson's related global research. Sometimes it seems that the directions are so similar but we know that some replication is necessary. Other times we see dead ends - also necessary because they may be avenues for other medical conditions.

We worry that laboratory focus will be lost in the fascination for the details. Perhaps we don't comprehend because we are not scientists but as people with hope and confidence. Perhaps it is the frustration level and the fears that keep us from understanding. Or we don't see an organization of information, a compilation of past and present knowledge, because it just doesn't exist.

Previously we have discussed the importance of recognizing and treating the precursor symptoms, of identifying biomarkers in order to delay onset, to implement preventative therapy. We've talked about proactive patients being good "teachers" for doctors because the patient has the motivation to search for more therapeutic information about his/her condition. While some patients rely totally upon the medical professional, these days many more realize that they must integrate the common experiences of others in order to find effective supplemental treatments. And still others step completely outside the box on the promise of a cure.

The beauty of patient experience is that it can open eyes to possibilities and potential as doctors begin to treat patients and not diseases. This is one reason that we go to every medical appointment with printed material even if it is a revised medication and supplemental list which explaines why, when, how each treatment is taken. Next we will add to a second list which explains changes in physical, cognitive and emotional condition. Many doctors do seem to hear better with their eyes...if they are going to take the time to listen at all.

Our perception of the Parkinson's knowledge base seems at times much like the assorted parts and pieces the blind men explore when surrounding the elephant while trying to describe it. Of course we need a complete description of an elephant, not an abstract simile nor an elephant by committee. That is where Sergey Brin of the Google team found himself when his genetic testing disclosed the same LRRK2 mutation exhibited by his mother, a PwP. Mr Brin has worked himself to a position where he has acccess to the resources to do something. He has means create the protocols to organize the data to see the patterns of the elephant. To bring, eventually, sentient life to the elephant.

It's Snowing All Over My Parkinson's

2010-12-17T18:42:00.002-05:00

Snow on birdhouse

WINTER DRIVING and PD

Before I got Parkinson’s I enjoyed winter, even a heavy snow storm. I often spent a lot of time working outside in winter months and my wife marveled at the way I could handle the heat of the summer as well as the bluster of winter.

Before PD, I was fascinated by the way the normal functions of society broke down. When I was a kid there was a heavy blizzard in the early 1950s with so much snow that. trucks couldn’t deliver to stores.The streets were plowed by the National Guard. Grocery stores couldn’t open. My mother and I walked about a mile up to the Main St and bought milk and eggs and butter.from some soldiers. Cars could not get through. My father didn’t get home from work until the next day. It was the deepest snow I’ve ever seen and that was over 50 years ago.

What the snow feels like with PD

My wife remembers that a bit farther north, milk trucks had to be pulled by horses for a few days. She and her friends actually dug a serious tunnel under the snow. The snow was way over her head even where it hadn’t drifted. She also loved those days when ice covered everything. Trees sparkled and yards were fairylands. For children, those days are magic.

About 25 years ago, I was often on call to deal with heating problems for the properties administered by the non-profit which I helped to found. I was out there on the road when few other vehicles were.

Our dog walk area in Winter

My wife still talks about the way I handled the car in a snow storm on a Christmas night returning home to Cleveland from Dayton. Most of the highways had been salted and although slushy were passable. She remembers the huge pink Caddy directly ahead of us at the crest of a hill, unexpectedly hitting unsalted ice and then sliding down sideways down the hill. The median strip looked like a demolition derby, 30 or more cars facing every direction. I had to steer from the icy road to the shoulder next to the guard rail protecting us from going over the side of the hill and then down the shoulder. Piece of cake for me. She says we’d still be in the median if she had been driving.

I hardly drive at all these days. The last time I drove in snow I had to get towed out of snow drifts at a shopping center near our house. I know my reaction times are a little slower but I can backseat drive with the best of them.

Sunset, trees and snow

Now bad winter storms give me anxiety and make me worry more about climate change, which many say is still just a theory and not a scientific fact. We’ll see about that.

Winter without climate change is bad enough, PwP worry about winter the way I do because we worry about anything that is change. My arm is stiffer and my hands shake Nothing helps very much except Sinemet and exercise and sometimes CoQ10 and relaxing. Those magic days become nightmares...and then Rita comes inside when I call her and I am rewarded with a smile and a nudge for a dog treat.

Isolation and Depression and Parkinson's Disease

2010-12-07T18:51:00.002-05:00

Another Try as A Year Goes Bye

It’s been about a year since my bout with dehydration. I managed to get through that horror with lots of prodding and insight from my wife/caregiver.

The Great Recession and my Parkinson's has drastically cut our income, so I no longer get a massage every week or go to the Nautilus room at the aqua center - that originally stopped with the dehydration. Because I could barely walk down the hall, let alone attend either exercise or massage, I simply could not attend. That was true for going to the local PD support group as well. After that the financial limitations became a harsh reality.

I’ve tried to keep up with exercise using my hand weights and cardio equiment at home. There are also chair exercises which we do to stretch, relax and use a few different muscles. I have never been a well-motivated person for exercise but the social aspect of the Center seemed to help me exercise regularly. Now I have to depend upon my own motivation to get me going.

Harry with the brothers a few years ago

You’d think that knowing it can help me live better and possibly longer would be enough but it isn’t. Sometimes I feel I have not left the second floor of my house for months - simply sitting at my computer without venturing out or seeing another human being besides my wife. The dogs have become my best buddies.next to what-ever hallucinations my brain has cooked up for me. Both dogs spend a lot of time near me...hoping for a treat but content to just be close. Blakey, the black cat, sits on my printer; while Mongo, the mama’s cat, still sleeps on my wife’s CRT.

I watch what’s happening to this country and I worry and despair. How can Congress go on vacation while millions of families have no wage earners? Politicians and even those people on the news and financial programs seem to be concerned with those who make $250000 rather than those who make $0.00. They give lip service to the rest but they have jobs, they are not on the ground floor. They don’t get it. I get the impression that they feel chronically ill people are slackers.

In the new Congress the conservatives want to cut spending when the economic situation demands that we increase it. We need to get out of Afghanistan and use the savings here. We need to leave scientists to do science instead of leaving it to ministers from bible colleges, online degrees or self-proclaimed. Could we cure PD sooner if we didn’t have one hand tied behind our backs?

Mongo and Blakey ready for winter

Note: When I first read Steve's words, I could see how damaging both depression and isolation can be for a PwP. Even before we recognized the dehydration, Steve was already shutting down the concept of straying too far from home. No trips to Lake Erie to watch the sunset. No shopping, no trips to the park to walk the dogs together. That was the fear setting in. No matter what I suggested, the answer was, "Not today."

We'll get him back to the therapy center once I''m sure that he will put in 100%. You can't just go through the motions when exercising. It has to be felt throughout the body And that only happens when you are there working for yourself.

He's making good progress just by getting the words onto the screen. And by reminding me that we are running out of dog treats. He's beginning to feel better about himself.

He has been helped by a few additions to his PD pill/supplement regimen.

Steve has now attended two monthly support group sessions and has walked with us at the park. He's getting out there again.

Mags

Glutamate, The Caffeine Gene, and the World Parkinson's Congress

2010-10-01T15:04:00.000-04:00

What are we learning about glutamate and Parkinson's disease?

There's good news

For years we've been asking restaurants to omit the MSG because we get funky headaches later after eating foods containing this excitotoxin. We'v been reading food labels to avoid monosodium glutamate. We were already working on an article about glutamate and the role this protein building amino acid and neurotransmitter plays in Parkinson's disease. We learned a little about the good, the bad and the ugly in the process.

We know that glutamate is a rapid, excitatory transmitter and that it can be associated to a vulnerability to addiction, so perhaps you could call it the smoker's nemesis. We also know that glutamate receptors are necessary for proper central nervous system functioning, for important cognitive function including memory formation and learning.

This week everyone is talking about glutamate and GRIN2A because of the news from the World Parkinson's Congress currently being held in Glasgow, Scotland.

The coffee cups are waiting

It has been learned that GRIN2A, is the "coffee" gene which when combined with caffeine intake appears not only to be neuroprotective for PD in a certain percentage of the population but may also affect PD clinical trial results when some study participants may have the altered GRIN2A gene. This in turn raises the question of whether it can also influence medications used to treat Parkinson's disease symptoms.

Those people protected by the caffeine gene are carriers of a specific variation of GRIN2A according to information discussed at the World Parkinson's Congress. At this time the focus is on a limited population.

We already know from the long Hawaii coffee study that people who had regular caffeine intake were (48%-84%) less likely to develop Parkinson's disease. It would be more than interesting to know how many members of this study also had the special GRIN2A gene version. But that was then and we didn't have the same technology or gene bank.

GRIN2A is a glutamate NMDA subunit receptor in a class of ionotropic glutamate gated ion channels, permeable to calcium. There has already been research about Bipolar disorder, ADHD and Huntington's disease as well as Parkinson's disease in connection to a hypoglutaminergic condition being involved in the pathogenesis. And certainly the negative role of glutamate in Parkinson's development is not unknown.

Researchers have been looking at the GRINB2 subunits for many years and their connection to PD in the forms of selective antagonists which can exacerbate levodopa-induced dyskinesia in animal models. In other animal studies it was discovered that loss of striatal dopamine led to an increased stimulation of NR2B aka GRIN2B which contains NMDA receptors.

Basically glutamate becomes a link in the nitric oxide chain. Under certain conditions glutamate can break through the outer cell membrane via the NMDA (n-methyl-d-asparatate) receptors located on the neurons. This creates a breach through which calcium can enter the cell. We already know that calcium is implicated in the death of dopamine neurons. If this chain can be interrupted...

To read more about the 2010 World Parkinson's Congress and to see folksy photos, check out Talk Parkinson's.

Additional reading:

Gene reference: GRIN2A

Netherlands twin studies

NMDA Receptors

Primate home range and GRIN2A

Following the Latest Stem Cell Debate in D.C.

2010-09-16T18:01:00.000-04:00

News from Parkinson's Action Network (PAN) 9-16-10

A few PD-related news updates

If you haven't read the 9/16/10 Parkinson's Action Network letter for the Senate Hearings on human embryonic stem cell research, here is a direct link to the hearings convened by Senator Tom Harkin.
What you will see is a video of the hearings convened to discuss the science not the legal entanglements or the preliminary injunction.

You can go to PAN to see the status of HR 1362 which is the National MS and Parkinson's Disease Registries Act. From the same page you will find the link to contact your legistlators: Help Make Stem Cell Research Legislation a Priority this Fall. It is not too late to contact your Members of Congress to express your concern.

If you missed some of the Podcasts offered through the Michael J Fox Foundation, it isn't too late to download them. We missed Dr Andrew Sngleton speaking on What Causes Parkinson'sDisease? so we'll be opening this download. You can still find the Podcasts listed under News & Events.

Lonnie Ali's recent remarks at a conference sponsored by GSK for PD patients and caregivers made it clear that the support of family and loved ones is so important to getting an early diagnosis. They were married a year after his PD diagnosis but 5 years after his parkinsonian symptoms were dx'd.

What we learn is that everyone does their part. If you can't be geographically close there is always email and the phone for quick contact. Just reach out.

Parkinson's Disease News Updates: August 2010

2010-08-25T15:33:00.016-04:00

For PD not all of the news is good but there is plenty of reason to hope

Beginning with the fun stuff. How good is it to hear that Michael J Fox will be appearing again on the small screen, accessible to us all. Sometime in or after September 2010 an episode of The Good Wife will air on CBS with Mr Fox as a guest star in the role of an attorney. You may not like the character he plays but we're looking forward to a performance to rival his outstanding work in Dennis Leary’s Rescue Me on FX.

About Cogane - not yet. The paper work for the Phase II Clinical Trials are being by prepared for submission to the FDA by Phytopharm. Phytopharm is a company which develops products from medicinal plants. Clinical Trial NCT01060878 is not yet recruiting in New York.

How is the pipeline doing?

There is no point in speculating on timeline to market because we’ve seen such nasty dates as 2013. Phytopharm is looking at two medications for Amyotrophic lateral sclerosis (ALS). One is Cogane and the other is a similar drug, Myogane, which already was awarded Orphan Medicinal Product designation by the European Agency for the Evaluation of Medicinal Products (EMEA) in 2008 following its orphan drug status by the FDA.

The financials for UCB look good this year with 63,500 patients in Europe alone using the Neupro Rotigotine transdermal patch. In the North America, Canadians and Mexicans can fill their Neupro prescriptions. This is not the case for those in the USA.

Mongo hates shortages

The Federal Food and Drug Administration (FDA) has an interesting web site where you can check current drug shortages. The site lists the drug name and the manufacturer as well as the reason provided for the shortage. The last UCB Neupro update was on 5/05/2010. The information provided: FDA has requested that UCB reformulate Neupro (rotigotine transdermal system) patches. UCB is committed to bringing Neupro to U.S. patients and has already made significant progress in the development of the new formulation.

Unfortunately there has been no actual update for PD patients since we last reported about the Neupro patch status. At the end of July, UCB announced the study results which demonstrated that Neupro had proved effective for people with moderate to severe Restless Leg Syndrome (RLS), 80% of whom often suffer from Periodic Limb Movement Disorder. The question remains, how will people with RLS and PLMD obtain the patch if they live in the US? See: our January 31, 2011 article for helpful links to the Neupro study for which you might just be eligible.

There does appear to be a Neupro Rotigotine Transdermal Patch clinical trial now recruiting. The NIH number is NCT00522379.

In our search for the latest information about UCB and Neupro, we came across a document which is worth a read in the light of public animosity towards big pharma. It is a UCB corporate 2009 publication: Patients, People, Planet, Ethics.

Road Closed again?

Stem Cell research has been dealt a blow by a splinter group and a Federal judge. The Obama Executive Order funding stem cell research has been hit with an injunction. You can read more of the recent story in this blog article by PZ Myers which references the New Yorker article which many have read. The basis for the injunction is the destruction of the embryo for research and means that the federal guidelines would need to be rewritten for those researchers receiving federal funding. Private research is not affected. Federal monies can be used if another lab supplies the stem cells. The basis for the injuction is the Dickey-Wicker amendment.

One of the best articles for explaining the injunction which grew from Sherley v. Sebelius can be found in the Jolt Digest of the Harvard Journal of Law and Technology.

For those following stem cell research news, you can read more at the Coalition for the Advancement of Medical Research (CAMR)

We found this Op Ed piece from the New York Times very interesting.
For more food for discussion and debate, take a look at Don C Reed's article "Overturn Dickey-Wicker Abomination, or Forget Stem Cell Cures" for a Generation at The Huffington Post.

For those PwPs concerned about a shortage of Sinemet (levodopa-carbidopa) we refer you to a public letter written to Amy Comstock Rick CEO of the Parkinson’s Action Network (PAN) by Michael Rosenblatt, M.D. Executive Vice President and Chief Medical Officer of Merck and Co, Inc. In the letter Dr Rosenblatt explains that the shortage arose as a result of changing the supplier of the active ingredient. The shortage was not due to a product defect. Generic substitutes which may not contain the exact proportion of the components but which are also safe and effective are also available.

September 2, 2010 addendum
You can read the 8/31/10 Motion to Stay filed by the Secretary of the Dept of Health and Human Services.
You can add your voice for support through Parkinson's Action Network and letters to your elected officials in Washington, DC. Just click on Take Action

September 9, 2010 addendum
Per an item from PAN: "...within the last hour the DC Court of Appeals issued a stay of the preliminary injunction halting federal funding for human embryonic stem cell research. It would appear that the stay is only in place while the full arguments about the request for a stay of the preliminary injunction are heard in the Court of Appeals, but the important aspect is that, for at least the time period that it takes for this next phase of the case, the injunction is no longer in place against National Institutes of Health (NIH) and funding can continue."

You can read a few more details at the NPR website

At the PAN website you will also see a link to VA information: VA Publishes Final Regulation to Aid Vietnam Veterans Exposed to Agent Orange
On August 31, 2010, The Department of Veterans Affairs (VA) published its final regulation establishing Parkinson’s disease, ischemic heart condition, and B-cell leukemias as service-connected disabilities for Vietnam veterans exposed to Agent Orange. The final regulation grants a 100% disability rating for Parkinson's disease, as well as retroactive veteran and survivor payments for qualifying veterans. There will still be a 60 day review period by Congress before payments go into effect.

The University of Maryland Medical Center recently published an article about the Parkinson’s disease diagnosis procedure. It is brief and worth a read for anyone with questions.

On the fun side, the American Parkinson Disease Association (APDA) recently published the Walk-A-Thon schedule for September and October 2010. Just scroll down the page to see 3 upcoming events.

Although the Parkinson’s Disease Foundation has not announced its next Expert Briefing or on-line educational events schedule, you can still access past seminars. The information remains both timely and helpful covering a broad range of information.

For many people with Parkinson’s, when the “off” times become too symptomatic, there is little choice but to add a COMT inhibitor to the levodopa-carbidopa mix. Stalevo is the medication of many who need to add entacapone to their l-dopa-carbidopa regimen in order to control the dyskinesia - dystonia which occurs. The FDA has now announced a safety review of a possible cardiac risk from use of Stalevo.

A bit off balance?

At Steve’s last neurology appointment he tried to discuss orthostatic hypotension (OH) with the doctor. The doctor was in agreement that the symptom could be PD related, medication related or a symptom exacerbated by medication(s). I think that he is waiting for us to propose something. We’ve mentioned Northera (TM) droxidopa before. I thought it was interesting to learn that Chelsea Therapeutics International, Ltd is now considering droxidopa for Chronic Fatigue Syndrome (CFS) as well as neurogenic orthostatic hypotension (NOH).

Droxidopa is a synthetic precursor to norepinephrine. Dopamine is also a precursor and it is thought that the serious symptoms of PD do not appear until norepinephrine neurons begin to decline in numbers. Currently in two phase III clinical trials for NOH in a number of conditions with primary autonomic failure as well as fibromyalgia and ADD for which it is in phase II trials.

If you are considering a Droxidopa Clinical Trial, there are several locations from which to choose.

Recently there was an announcement that a study by the NeuroGenetics Research Consortium has found a there is a link between immune system gene variants and Parkinson’s disease. This particular study led by Haydeh Payami has been active for at least 20 years. Based upon the study results closer scrutiny will be given to “the possible role of infection, inflammation and autoimmunity in Parkinson's disease.” Other Parkinson’s specialists have long proposed the possibility of PD as a disease on inflammation.

Then there is the news about the search and discovery of LRRK2 blockers for patients with mutations of that overactive protein which appears to cause neuron death and consequently PD. Two medications were found which appear to block LRRK2 and to prevent neurotransmitter death in lab rodents. Hence is a new target for treatment development.

On a personal note: Steve has been trying another herbal supplement. Huperzine A is a low level acetylcholinesterase inhibitor for improved cognitive function. It has been a few weeks and we have not seen any negative side effects although we have seen some positive effects, so we plan to order another bottle from Swanson.

We do realize that this is really an Alzheimer's disease (AD) supplement rather than a PD supplement so we are watching carefully and will probably stop for a few weeks to observe changes.

If you are interested in Clinical Trials with open recruiting for Parkinson's Disease, check the NIH listings. You can select MAP in order to find trials in your area.

At this Clinical Trials.gov page you will see a wide variety of PD specific trials now recruiting in such area as Transdermal nicotine patches, Transcranial Magnetic Stimulation (TMS), Overactive bladder, Urate elevation, antidepressants, Rivastigamine Patch, Rasagiline (Azolect) as an add-on to dopamine agonists, effect of exercise, Safinamide, Non9nvasive Brain stimulation, Memantine for gait and attention deficits, Ropinerole (open label), facial expression, efficacy of voice treatment, CoQ10 (there is also one for Huntington'sdisease), SAM-e, biomarkers, Naltrexone for impulse control disorders, Isradipine (Dynacirc), green tea (polyphenols), Vitamin B12, Apathy, Swallowing Training. In all there are 274 open trials although not all are recruiting yet.

One last note: the PD-chocolate trial is only being conducted in Germany at Dresden University of Technology. On a personal note, some of us are waiting for the caregiver trials involving fine chocolates.

Webinars and Webcasts of Interest for Parkinson's Disease

2010-06-22T12:15:00.002-04:00

For PwPs, Caregivers and Families:
You might be like to attend these online events

Drug Development Pipeline on Thursday, June 24th, 2010

2:00 pm to 4:30 pm EST

Direct from the Campus of Georgetown University, Parkinson's Action Network (PAN) is hosting "Emerging Therapies: From Microscope to Marketplace" featuring a panel of speakers from the scientific community. Each will address a different stage in the drug development pipeline process.

Howard Federoff, M.D., Ph.D.: Executive Vice President for Health Sciences and Executive Dean of the School of Medicine at Georgetown University will moderate.

The panel:

James P. Bennett, Jr., M.D., Ph.D.: Chair, Department of Neurology and Founding Director of the Virginia Commonwealth University Parkinson's Disease and Movement Disorders Multidisciplinary Research and Clinical Center

Story C. Landis, Ph.D.: Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Raymond T. Bartus, Ph.D.: Executive Vice President and Chief Scientific Officer, Ceregene, Inc.

Jackie Hunt Christensen: PAN Minnesota State Coordinator and Clinical Trial Participant

Janet Woodcock, M.D.: Director, Center for Drug Evaluation and Research, Food and Drug Administration

Registration is not required. On the day of the Webcast, simply visit the PAN home page and tune into the Webcast from your home or office computer.
For more information on the Webcast, please e-mail PAN

Registration is not required. On the day of the Webcast, simply visit the PAN home page and tune into the Webcast from your home or office computer.

~~~~~~~~~~~~~~~~~~~~~~~~

From AARP on the same day, Thursday, June 24, 2010

"The New Health Care Law: What It Means for People with Medicare"

Times are:

2:00pm -3:00pm EST

1:00-2:00 pm CST

12:00 pm-1:00 pm MST

11:00 am -12:00 pm PST

To register at AARP for this event, click here

There will be a Question and Answer period with AARP experts

~~~~~~~~~~~~~~~~~~~~

Did you miss one of the Parkinson's Disease Foundation (PDF) Educational Events?

You can see and/or hear them here.

Changing Stages of Parkinson's Disease

2010-06-09T14:51:00.003-04:00

I'm Back

This is the first article I have written for my blog in almost six months. After eight years of having Parkinson's disease and treating it fairly successfully with medication, alternative medication and nutritional supplements, exercise, massage and diet changes, I ran into trouble between Thanksgiving and Xmas last year. I thought they were symptoms of PD.

The urinary symptoms which had been under control were no longer controllable; perhaps because I was neglecting to take the herbals which had helped for so long. Suddenly I had to urinate really frequently and didn't always make it to the bathroom even though my bed is only 20 feet away. I became afraid to leave home for fear of being too far from a rest room. Vivid dreams occurred so often that I could not tell what was real and what was not. My overall memory of this period is vague but I felt as if I were dying.

Although I primarily stayed in bed, often I thought I was someplace else and worried about how I was going to get home. In an amazingly short period of time I went from the early stages of Parkinson's to an advanced state; it seemed to take 2 or 3 weeks. (Editor's comment: it was practically overnight)

How did I get to that state?

In early November I had an appointment with my primary care doctor to discuss some alternative treatment options. He referred me to the neurologist to continue this discussion. The urinary issues were not discussed although we did discuss my arthritic knee and the loose tendons. One area of concern for me was the MRI he proposed. I do not like MRIs. I do not like being in places which I cannot leave of my own free will.

Even the open MRI which I was supposed to have done years ago, did not take place because it was too stressful for me. This doctor suggested that we could begin with an Xray and take it from there. He gave me the lab order but I was too shaken by the mere mention of an MRI to do even that.

We made the neurology appointment as suggested and then my wife decided that the Xrays had to be done before that appointment in three weeks. She finally nagged me to the lab for the Xrays a few days before I was to see the neuro. That weekend I hardly slept and the urinary issues were getting worse. I wasn't eating as much and had been limiting my coffee and tea intake because of the urinary frequency and urinary hesitancy. As a matter of fact, I was limiting all fluid intake. No fluid - no urinary frequency - no problem. But there was a problem and the frequency urges did not stop.

By the time we were talking to the neurologist, the transition was taking place. I asked not for the intended alternative treatment but for Sinemet which I thought would help the urinary issues. He agreed after the routine PD testing. By the next day the nightmare was developing full force.

Almost overnight I was having difficulty walking down the hall. I could barely stand erect. Cognitive skills were muddled by hallucinations and illusions. I needed assistance to get into bed, instructions just to roll over. I needed help pulling up the blanket. Dressing and bathing without help was impossible. I would get up to eat but continued to drink only enough liquid to swallow a pill. I recognized the woman who prodded me about drinking more water during the day as being very similar in appearance to the woman who responded to my nightly hollering for help. Who was she? This nurse gave me my wife's name when I asked. What was this place?

My wife, meanwhile, was learning what you need to do to get a doctor's secretary to relay the seriousness of a condition. Because I had signed a release allowing the office to speak to my wife about my care, she knew she was on safe ground there. Her early calls were partially successful. The primary care office called back to refer her to the neurologist. The neurologist called back to say that Parkinson's disease can't go through such a short term transition and so we were looking for another cause possibly a UTI...and referred her back to the primary care doc.

She made the appointment for the following Monday and sat down to think and to discuss the issue with the massage therapist when she called to cancel my appointment. Sleep deprivation was only part of the problem. So she gave me cranberry capsules insisting that I drink more water. For half a day, I had a return to normalcy. And she had an insight. I was dehydrated.

When we went to the doctor's appointment, she took my urine specimen along. She insisted that it be tested. When it came back negative the discussion turned to prostate issues. We left with sample bottles of Flomax. What we didn't know was how long it would take before the Flomax would work - that it actually would be another 5 weeks before for the compulsive insistence that she walk me to the bathroom every 20 minutes would stop.

The dehydration issue was caused by the enlarged prostate which I knew about but didn't discuss much. Years earlier I didn't want to take the meds and had found relief with herbals. But this time I had confused the prostate problem with PD which exhibits the same symptoms. I'm an older man, older men frequently develop prostate issues. Had I talked to my new doctor about the problems instead of accepting that they were part of the disease, I wouldn't have had to endure all of this. The damage done by the dehydration, the stress for all of us except the cats - the dogs were very subdued during the first month - was intense.

It has been a long recovery and we learned a few lessons and revisited a few others.

1) Protective underwear is cheap in comparison to losing 4 productive months.

2) Sign that doctor's release now so that your spouse or other family member can talk to the doctors office

3) Don't make that call or visit the doctor without a complete written list - make copies

4) Symptoms of dehydration and sleep deprivation are similar to dementia and to PDD

5) Ask how long it will be before you can expect to feel results from a medication

6) If a nutritional supplement helps, don't stop taking it just because there are so many pills to take

7) Don't assume that the problem is caused by the Big Problem;there can also be other medical issues - tell your doctor.

8) Just because a doctor prescribes it, that doesn't mean you shouldn't do your own research for contraindications. (I have a faxed-in prescription that we will never fill for just that reason - my wife did the homework)

9) All of you caregivers out there deserve more credit than you receive!

10) Be persistent - it can be depressing - don't give up.

How Much Antifreeze Does a Parkinson's Patient Swallow?

2010-05-08T18:56:00.002-04:00

What the Heck Is in My PD Medication and Why?

A serious issue for people with Parkinson's disease is those times when medication wears off before the next dose is due.

Remembering to take the first dose in the morning but sometimes forgetting the next one can be a problem as well.

That's why there are pills specially designed to address and correct/remove those problems. We know them as timed release, controlled release (CR), sustained release (SR), extended release or long acting ER, XR, or XL), slow-release, and continuous-release (CR or Contin).

We know we can't chew them. But else do we know about how they work? What makes it possible for this timed-release to occur after the pill is swallowed? Is it safe?

And when we looked at the ingredients of these shinny pills. Sometimes there is polyethylene glycol (PEG) or ethylene oxide which we know is a precursor to ethylene glycol ... antifreeze...or we see propylene glycol and butylated hydroxytoluene. We learned that part of the latter is a solvent. What's the story here? Why is this stuff in a pill which is supposed to help? How is it used?

We know that when treating certain medical conditions it can be helpful to have a medication which can be released slowly and steadily throughout the day in order to maintain a constant blood serum level of the medication. Controlled release drugs have an advantage of being somewhat cost-saving and many may actually release a safer level of the medication. Most do this fairly well; a few have unresolved issues.

The mechanism of burst-release still needs refining because on occasion more medication is released than designed. New technologies are developing which will use not polymers but possibly recently developed polypeptide agents possibly utilizing RNA and/or siRNA (small interfering RNA). Not yet, but perhaps within a few years. In London at the end of the month there will be a specific presentation for "Controlled release in chronic diseases" at a controlled release event. And we would expect these pills to be safer as well as having a higher efficacy rate.

The mechanism is that either the drug matrix dissolves slowly and steadily or that the drug is released cyclically over a long period. The formulations may vary from chitin to acrylic to polymer based tablets with a porous membrane on one side with different processes occurring once in the body. The bursts seem to occur in the CRs but perhaps steadier control will be possible in the future.

But what about that other stuff?

According to what we've read, polyethylene glycol (PEG) - as used in medications - has a low toxicity "When attached to various protein medications, polyethylene glycol allows a slowed clearance of the carried protein from the blood. This makes for a longer acting medicinal effect and reduces toxicity, and it allows longer dosing intervals." This would explain why it is in the Extended or Controlled Release pills. Is it totally safe? Apparently for now it will have to be safe enough. Even taking several pills of this type a day should not become an issue unless there is a intestinal blockage.

The differences between PEGs are molecular weight. What about polyethylene oxides (PEO)? We know that PEs are carcinogenic at certain ppms. But we are not chemists and that is an area for the experts to discuss.

These chemicals are sometimes used in laxatives and calcium channel blockers. The calcium channel blockers have a semi-permeable membrane which surrounds the actual drug. The core itself is bi-layered with the active layer of the medication and an inert layer, known as the "push" layer of an osmotic. And this is where we find the PEO polymer. The push layer will swell and force the active drug out of the membrane through a pre-drilled laser opening on the active layer side of the membrane. This creates a fairly steady release of the active chemicals into the gastrointestinal tract.

What happens to the inert but actively working push layer when emptied of the active drug? It's already in the intestinal tract and so is simply taken out with the trash.

In laxatives, osmotics create excess water in the intestine to loosen stool buildups. Taken with an electrolyte solution osmotic laxatives are often used prior to bowel surgery. Some of these contain polyethylene glycol and are intended for short term use only. Some Parkinson's patients take Polyethylene Glycol 3350, an osmotic laxative, in the form of MiraLax or Macrogol for constipation as a last resort because nothing else works for them. The caveat is that too much or too often can result in diarrhea. Side effects include nausea, gas and bloating.

There is no question that it is not a good idea to take any medication with polyethylene glycol if you are allergic to it as it can cause rash, swollen tongue, hives and other typical unpleasant allergy reactions.

Do not confuse ethylene glycol (EG) with polyethylene glycol (PEG). They are not the same thing. Ethylene glycol is metabolized into oxalic acid, a poison that affects the brain, the heart and the kidneys. Ethylene glycol (EG) is toxic to people and to pets. Your car is happy with it because adding it to your radiator offers protection in cold weather. In your body it can kill. Polyethylene glycol makes your intestinal tract happier because it can get rid of toxins. In your body it has low toxicity.

Propylene glycol, an organic compound (a diol or double alcohol) is used as a humectant (moisture retentive) food additive E1520, as a moisturizer in medicines, toothpaste, mouthwash among others. While it does have similar properties to ethylene glycol and is used in antifreeze and de-icers; it is less toxic. And of course, toxicity would depend upon the percentage used in a product. It metabolizes to pyruvic acid, as part of the normal glucose metabolism process. Although long term toxicity is low to humans; it can be toxic to dogs and cats (although the effects are apparently different in cats). Do note that this type of alcohol is different than that which you have in a drink.

Who else has weighed in? From the CDC we learn that the FDA classifies polyethylene glycol as an additive that is "generally recognized as safe" for use in foods. In large quantities it will increase the acidity of the body. What is does not do is to form the harmful crystals which collect to the kidneys as ethylene glycol produces while it breaks down. Polyethylene glycol breaks down rapidly in the body.

Although most of the warnings we saw related to overdose of the medication itself and not the individual components, this does not mean there is not room for improvement. As more is learned about our air, water and food, we think that more attention will be directed to medicines. It may happen very quietly within the pharmaceutical companies because of economic impact. At the same time, the drugs taken for Parkinson's disease are immediately necessary in their available forms and changes co$t.

By the way, the chemicals are also found in most toothpastes.

Note: The title question is in part rhetorical, however, the answer would be based upon each individual's medicine cabinet. We looked at DynaCirc CR and Nimodipine labels for this article.

Additional Reading:
American Academy of Neurology, Quality Standards Subcommittee guidelines - published Neurology. 2010;74:924-931. http://www.medscape.com/viewarticle/718759

Long term efficacy study 2000 placebo/blind small doses of isosmotic PED electrolyte balanced solutions over 6 months was an effective constipation treatment; "appeared to be safe,tolerated and devoid of significant side effects"

More about polyethylene glycol at Wikipedia

Ethylene vs polyethylene glycol

Butylated hydroxytoluene, a lipophillic (fat-soluble) organic compound that is primarily used as an antioxidant food additive as E321

From the CDC:

Polymers in Controlled Drug Delivery by Lisa Brannon-Peppas

Drug Release from Hydroxypropyl Cellulose and Polyethylene Oxide

The Use of Polyethylene Oxide Mixtures to Study Formulation Robustness in Hydrophillic Extended Release Matrix Tablets

Formulation of a Model Poorly Soluble Drug with Low Molecular Weight Grades of Polyethylene Oxide demonstrates Improved Aqueous Solubility

More information about constipation

Neupro Rotigotine Transdermal Patch Ordered Back to the Drawing Board

2010-04-29T23:41:00.004-04:00

Parkinson's disease and Restless Leg Patients Will Have to Wait - FDA Has Ruled

The news for US Parkinson's Disease patients waiting for an early FDA clearance of the Neurpro patch formulation is not good. On April 23, 2010 UCB announced the receipt of the FDA response letter. The FDA informed UCB Pharma that it will have to resolve all crystallization issues with the Neupro® patch. Apparently the policy is zero tolerance despite the fact that the patch was returned to the European market about 10 months ago.

We already knew that if the patch received approval (again) from the FDA that there would be a delay while the new patches were produced. In all likelihood, the news would not have been officially released until the patches were on their way throughout the US to pharmacies for cold storage. This delay would have put the availability back to the end of 2010.

With the decision to order UCB to find a definitive solution to the crystallization issue which did not appear to negatively affect users, UCB will be back to redesign. The FDA acknowledged that the new refrigeration conditions - the cold storage distribution would "significantly inhibit the degree of crystallization on the batches but" the order is to reformulate the product to definitively resolve the issue.

From the 4/23/10 announcement: "We have already been working on a room-temperature stable, improved formulation of Neupro® and have made significant progress in this area," the Chief Medical Officer of UCB added. "Neupro® has made a meaningful difference for many people with Parkinson's disease and Restless Legs Syndrome. We are committed to obtaining FDA approval so that people in the U.S. who live with these diseases can benefit from Neupro."

The good news for PD patients around the world with the exception of the USA are the results of the RECOVER study were presented in at the American Academy of Neurology annual meeting in Toronto, Canada in April, 2010. The data demonstrated the rotigotine improved both early morning motor function and improved non-motor symptoms in Parkinson's patients. Symptoms such as sleep, mood, cognition and pain were measured and found to be improved. Nocturia, night time excessive urination remained unchanged and there were some adverse events such as site reactions, nausea and dizziness in both the rotigotine group and the placebo group. Rotigotine was shown to be effective up to 6 years and provided improvement in movement symptoms for up to 6 years.

In another study the Neupro® Rotigotine Transdermal Patch was shown to provide sustained benefit for Restless Leg Syndrome.

One thing to remember is that rotigotine is a dopamine agonist and as such there are also side effects. It is unlikely that reformulation will alter those side effects because of the class of the medication. For the people who have been helped by this medication, its loss was quality of life altering.

Based upon the fact that reformulation could take at least a year or two and FDA approval would probably take as long as their denial, it may be 3 years before it is seen again in US pharmacies. After approval, there would probably be a significant period of time to begin manufacturing and distributing.

We wonder why the the FDA did not allow for a provisional approval for, say 2-3 years, while UCB worked to meet the present requirements. Based upon the fact that the medication is on most of the world market already, it would be the humane thing to do.

On a personal note, we'd like to apologize for the delay in posting the Neupro-FDA information. I found it so upsetting, that although Steve gave me the information immediately, I couldn't find the words to express my disappointment.

Previous Neupro posts:

March 14, 2010

On 3/11/2010, 12/23/2009, 12/11/2009

November 26, 2009 in a Thanksgiving hope

August 16,2009

April 10, 2009 in which we included many links about the patch.

Coping with Problems of Postural Instability in Parkinson's Disease

2010-04-22T19:41:00.012-04:00

Preventing those PD falls and What to do when you do fall

In the TRAP of Parkinson's disease, postural instability is the last of the big 4 symptoms. It is also the symptom which can lead to one of the leading causes of death for PD patients.

Postural instability can be caused by Parkinson's disease or can be related to syncope (fainting); orthostatic hypotension as a side effect of medications taken either for PD; neurogenic orthostatic hypotension as a result of a condition such as MSA; a cardiac condition, medication-induced dyskinesia, or another issue. Postural instability can also be a byproduct of depression for which PD does not lack.

Because there is little help through medication, that leaves devices, caregivers, exercise and the patient to recover from a fall or to better train the body to withstand the problems of postural instability.

Although I do not trust a lightweight walker for stability in heavy lifting, it might be of value if that is all that is around. It can be used for the patient to pull himself/herself up if someone is present to stabilize the walker. Otherwise both patient and walker could fall over. A cane with those extra legs at the bottom might do the job if there is arm strength.

There is also value to having handrails installed in hallways and even bathrooms just as they are on stairways. Avoiding backless chairs or stools is also advisable in order to avoid the risk of retropulsion - leaning back to regain balance or because of loss of balance with the resultant fall.

One important aid is exercise. Gait exercise can be crucial. We suggest asking for a referral to a therapy center so that gait training can be initiated. Gait training would include lengthening of stride, learning to open at the hips for a wider stance. The smaller the space between the legs, the less option to maintain balance. Lifting the legs almost in a march rather than shuffling and sticking to the floor may also be of value to provide a mental and physical cadence and to decrease the risk of the tripping on the shuffle.

Exercise addresses range of motion, flexibility stretching and yes, even strength training (to assist in rising if you do fall) and breathing. Yoga and Tai Chi exercises can help with balance and even graceful falling. Nautilus is important exercise equipment and there are less expensivel pieces of exercise equipment which can be purchased for home use. Don't neglect hand exercises. Being able to grip is crucial; a weak or claw-like hand won't help you.

Dance therapy might be helpful. Although its effects will not be physically apparent after the music stops, there might be a psychological-confidence effect which impacts postural instability due to PD depression. And it's FUN! Even in your living room. Get those endorphins going.

Locate a therapy center which has Forced Exercise equipment and aqua therapy. Water exercises can be beneficial to a PD patient because of the buoyancy effects of exercising - marching in the water. And Forced Exercise - not on a treadmill in this case unless there are trained spotters or with a support vest which attaches to the ceiling - but on the motorized exercise bicycles which compensate for the patient's inability to maintain the necessary rpms on his own. For some people these bikes are an affordable option for home use - for others, they are not. But the bike must be able to maintain between 80-90 rpm. There are two types of therapeutic bikes for this purpose. One is the Theracycle (there should be an ad link on this page). The other company is Reck MotoMed which makes several styles for home and therapy center usage.

Naturally there are aids such as shower seats (with backs or transfer seats), grab bars in the tub/shower area (no suction cups please), hand-held shower-heads with longer hoses and on-off buttons to prevent unnecessary standing in the shower. Soap on a rope.

No PD home should be without bath/shower aids even if they are not needed immediately. Knowing how to use them and using them regularly helps to train the body so that when the equipment is needed, there is kinetic memory to reinforce the use patterns. (Yes, I am a believer in the possibilities of kinetic memory to resist the tightening muscles and we have seen it work with my husband in entering/exiting the shower after the side effects of dehydration - another story - had some temporary but dire cognitive effects).

Little is available to address postural instability in PD. Usually discussed as a later PD symptom because it is apparent then, to many it is an invisible side effect as a very early symptom. Everyone talks about falls, the risks, prevention and the role they play, but we haven't found many solutions to address the problem by fixing the chemical imbalances which cause it because we are not sure precisely where in the brain the problem originates although the focus is on the brain stem.

There is one rather expensive pneumatic device which can be used in the home to aid in lifting and there appear to be patent applications for more. The link to this inflatable device is provide below at a site with which we are unfamiliar.

Have a home safety evaluation conducted. These are often done by occupational therapists - they'll survey the home, watch the patient functioning in their own environment and make safety recommendations. They need to know the patient has fallen in the past and what the ensuing problems have been.

The process for assisting a patient who has fallen is step by step after you are sure there has been no injury. Do not move an injured person. Make the call for emergency medical assistance. Or use that MedAlert button.

No injuries? Whew! Let's catch our breath. Everybody breathe calmly a few times to relax.
Encourage the patient to roll from the landing position to a prone face down position. You may be able to assist with that.
Next the patient must raise the upper torso onto bent arms. The lower part of the arm is on the floor.
The buttocks are next, assisted by the knees.
With weight on the forearms, rock forward and then back as you use those abdominals to lift your butt into the air.
The knees will walk forward and assist with the push up.
Once the patient is on his/her knees, you can assist them if they need help. If they are unable to rise from a kneeling position, they may be able to pull up on sturdy furniture or walker. Or you may be able to brace them (their arm around your shoulders and both of you rise from a kneeling position. The caregiver must keep a straight back to avoid injury.
If you are alone, you may be able to crawl on your knees to furniture solid enough to provide support for the pull to a standing or seated position.
At this point prevention and exercise seem to be the best methods to reduce the risks. Many caregivers are simply not strong enough to pull or lift a person lying on the floor without assistance. This is also another argument for the other forms of exercise accompanied by strength training.

additional reading:
Chronic Dizziness and Postural Instability
Repetitive training of compensatory steps:
Forced Exercise to Relieve Symptoms of Parkinson's Disease
Postural Instability in Idiopathic Parkinson's Disease

Links to inflatable device and detailed advice on its usage:
Same information if you can't view pdf format:
http://docs.google.com/viewer

It's being called WiiHab and we already know that it can help with PD depression, what about postural instability? As a diagnostic it has been found to be effective:

Nintendo Wii Balance Board Could Prevent Falls

Validity and Reliablity of the Nintendo Wii Board for Assessment of Standing Balance

To try the Wii at home: you'll need the Nintendo console, the balance board and some accessories such as the WiiFit program and controllers. The balance board must be on a firm surface to work properly. If balance is a serious problem, make sure you have support or supporters handy.

For more information check Wikipedia before you buy

Is the Plug Being Pulled on Embryonic Stem Cell Line Distribution?

2010-04-12T23:23:00.002-04:00

National Stem Cell Bank NIH Contract Not Renewed - WiCell Plans to Move Forward
How Will This Effect Parkinson's Disease Research?

The hope for the use of stem cells to treat and possibly cure many incurable diseases or life-altering conditions is shared by many patients and families around the world. Research with human embryonic stem cells (hESC) is still relatively new, having been started at the University of Wisconsin-Madison in 1998 in the lab of James Thomson. Despite the apparent opening of the field upon the Obama orders to the lift the Bush ban against federal research funds being used for hESC, the new NIH guidelines were not met with overwhelming enthusiasm. Still restrictive, these guidelines did, however, open the door for researchers. Now, a few months later, it would appear that door is subtly and quietly being closed again.

The National Institutes Of Health (NIH) did not renew the National Stem Cells Bank's $16.1 million four year contract with WiCell Research, a private non-profit at the University of Wisconsin-Madison. The contract, which expired on February 28th, 2010, had subsidized the distribution of Federal approved embryonic stem cells. Since the contract was not renewed, the lack of action and adequate funding caused the bank to regroup. The closing has led to a doubling of the price for approved stem cells. Costs have risen from $500 a vial to $1000 as there is no longer a subsidy for obtaining those 20 lines.

Both the general public and medical scientists had thought that stem cell research would be moving much faster after President Obama took office and doubled the number human embryonic stem cell (hESC) lines available. Instead, just getting the lines distributed to the researchers has become an unexpected hurdle. The former National Stem Cell Bank has now become the Wisconsin International Stem Cell Bank (WISC Bank) but the prices have been doubled in order to meet previously subsidized expenses. It is not clear how this will effect future research. WiCell has, however, expanded its lines from 20 to 33 and is planning to move forward.

Is there an underlying reason to attempt to bar one door in favor of another to open wider for another area of research? We don't have that answer; the transition seemed low-key. But there in recent years there has been an expanding a trend toward not the scientific significance but rather the economic impact of research. Science, politics and finance do not make a great martini; but they do make the research drink in which currently we find ourselves.

In January NIH expanded its contract with a different cell bank. Coriell Institute for Medical Research is a non-profit institution which established the Human Genetic Cell Repository in 1972. Coriell is known to have the largest bank of human cell lines and has long been associated with the NIH. In 2010 the National Institute of Health provided $27 million to Coriell for banking induced pluripotent stem cells(IPS), for which there is no destruction of embryos, to create a stem cell lab and a human genetic biobank. Nothing is planned at this point for specifically underwriting embryonic stem cell banking.

The hope is that the NIH will continue to consider setting up its own public stem cell bank if they are not going to renew with WiCell. This action would reduce the price and speed the delivery of all lines but especially the new lines approved by the Obama administration.

Currently there are 109 hESC lines awaiting NIH approval for NIH funded research, 237 lines for which there is an intent to submit. 51 hESC lines (3 on hold) are available in the NIH Registry. The approved lines are eligible for NIH funding grants but these lines are available only through individual institutions. A total of 54 institutions have submitted lines or intend to do so. The future costs per vial for researchers is unknown although currently Children's Hospital Boston, affiliated with Harvard Medical School which is still shipping lines at a loss.

While there are many big pharma potentials, it is the preliminary and intermediate work in understanding the medical conditions, recognizing the best targets, developing safe and effective processes and procedures that must take place before there is more than profit potential. And after that the intellectual property rights will have to be determined and the debates will rage.

Waiting for effective treatments are people with Parkinson's and Alzheimer's disease, diabetes, heart disease, spinal cord injury and many more. For these people with incurable conditions has a hope been dashed or simply redirected to another area of scientific research? Time, once more, may not be on our side.

References:

The Scientist.com

Wi Cell.org

NIH Telethon Network of Genetic Biobanks

Nature.com

Another Look at Stem Cell Research by Dr Alan Malnak

About the Coriell Institute for Medical Research

Promises, Promises by Stuart Blackman, The Scientist

You can read more about stem cell basics at the National Institutes of Health website. You can also read the 2006 NIH Stem Cell Report of progress made since 2001.

Calcium Channel Blockers Crossing the Blood Brain Barrier for Parkinson's Disease

2010-04-07T14:55:00.012-04:00

BBBs and the L-type CCBs that cross them

If you've ever looked at the common questions about Parkinson's disease and dopamine as asked in the classroom or in homework help on Yahoo!Answers, you have already seen the most common question goes something like, "Why does dopamine die in PD?" And that's a biggie, misleading but still a $64 million dollar question.

One interesting thing about Parkinson's disease is that although dopamine is produced in several areas of the body including the brain in the substantia nigra and the ventral tegmental area, the VTA does not appear to be susceptible to overexpression of alpha synuclein. Which means there is yet another research area for the potential of grafting - or stem cell therapy. Moreover, not that much dopamine is metabolized to norepinephrine which explains why PD may not begin officially until the number of norepinephrine neurons also diminish.

But that's not our question for today. What do we know know about saving dopamine neurons in the substantia nigra?

Mouse PD models have already demonstrated that cell "rejuvenation" protects neurons in studies at Northwestern University. Most human cells use either potassium or sodium channels when they are young but as the body ages, the dopamine cells switch to calcium channels. By blocking the calcium channel may give the cell a chance to rest and recover which is healthier than cell death and essential for PD. In 2007 Steve read at least two abstracts by Dr DJ Surmeier etal about this very subject.

In the first abstract it was the statement: "Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression."

And in the second:

"The Ca(2+) channels underlying autonomous activity in dopaminergic neurons are closely related to the L-type channels found in the heart and smooth muscle. Systemic administration of isradipine, a dihydropyridine blocker of L-type channels, forces dopaminergic neurons in rodents to revert to a juvenile, Ca(2+)-independent mechanism to generate autonomous activity. More importantly, reversion confers protection against toxins that produce experimental parkinsonism, pointing to a potential neuroprotective strategy for Parkinson's disease with a drug class that has been used safely in human beings for decades."

In order to stay on target we have to mention the arguments.

From DJ Surmeier in Neuron: "The controversy about whether dopamine contributes to cell loss in Parkinson's disease takes a new turn as Mosharov et al. in this issue of Neuron demonstrate that Ca²⁺ influx through L-type channels elevates dopamine synthesis to potentially toxic levels in vulnerable ventral mesencephalon neurons."

In the study entitled "Interplay between Cytosolic Dopamin(e), Calcium, and alpha-synuclein causes selective death of Substantia Nigra Neurons"
"They attribute this specific elevation of cytosolic dopamine in SN neurons to the presence of a pace-making L-type calcium channel as a source of calcium entry, present in SN, but not VTA, neurons. Blockade of this channel, as well as treatment with intracellular calcium chelators protects SN neurons from cytosolic dopamine build-up....the pace-making L-type Ca channel may prove to be a useful therapeutic target in PD"

Faculty of 1000 Biology: evaluations for Mosharov EV et al Neurorn 2009 62 :218-229

We've written before about the studies which found that neurons die because calcium channels lead to an increase of dopamine inside the cell; excess dopamine then reacts with alpha-synuclein to form inactive complexes; and then the complexes gum up the cell's ability to dispose of toxic waste accumulating in the cell over time. The waste eventually kills the cell. Put another way, Dopamine in presynaptic terminals prior leaving the vesicle, signal the post synaptic terminal. "A better treatment may be to push more dopamine into the compartments where it has no toxic effect on the cell" according to Eugene Mosharov, Ph.D., associate research scientist, and David Sulzer, Ph.D., professor of neurology; psychiatry at Columbia University Medical Center.

The question is why? And that is the answer being sought in the Calcium Channel inhibitor research - does the Ca inhibitor restore a more youthful saline condition to the cell in order to prevent cytosolic death? And if so what is required of that inhibitor? It has been proposed that the inflow of calcium is the last pathway "for irreversible neuronal injury" because the oxidative stress of free radicals "prevents neurons from maintaining ionic homeostasis." One result is that neuronal depolarization triggers an action potential which opens the Ca channels. So what we need is a way to prevent the floodgates from opening to cause that neuron damage.

The first thing that this CCB must be able to do is get to the brain in order to work. Crossing the blood brain barrier (BBB) depends upon lipid solubility of small molecular size. To be lipid soluble means that it must be rendered more polar by metabolism prior to excretion in urine. Where can we find those small lipid soluble molecules?

Within the dihydropyridine class of CCBs is a subtype of L-type (L representing long-lasting length of activation - slow CA channels in the cell membranes) voltage-gated calcium channel blockers. These L-type Ca blockers exert an anti-inflammatory effect and we know that some scientists have referred to PD as an inflammatory disease. As it happens, neurons which die in Parkinson's also contain a type of L-type calcium channel. CCBs affect SN neurons in a manner similar to the way they affect the heart.

Now it happens that the channels are not identical. In the substantia nigra we find a CaV1.3 channel. The current drugs in the L-type class happen to prefer CaV1.2 channels so we aren't there yet. As a matter of fact, there is an open door for more R&D in this area. But if you have PD, you often try what is available.

Research at Northwestern University, at Emory University, at Columbia University may find the precise answer. Meanwhile at Northwestern Dr Surmeier has explained, "...partial blockade of Cav1.3 channels is sufficient to provide protection against a toxin challenge... We also know from epidemiological studies (Becker et al., 2008 and a study by Ritz et al. in press) that dihydropyridine use for hypertension is associated with a significantly reduced risk of Parkinson’s disease...If it turns out that more complete antagonism of Cav1.3 channels is necessary to achieve protection in humans, then more selective drugs would have to be developed that spare the cardiovascular system."

Of the dihydropyridine class (note that they all end in "dipine"), the L-type inhibitors which cross the blood brain barrier are: Amlodopine, Azenlnipidine, Clevidipine, Felodipine, Isradipine, Nicardipine, Nefedipine and Nimodipine.

additional reading:

Neurons and action potential - scroll down the page

Neurotransmitters and their molecules

Brain diagrams: the basal ganglia and the cerebellum

Previous posts and comments:

The PD Triangle for cell death

What I Did when DynaCirc Wasn't Available Nifidiac vs DynaCirc: my experience

DynaCirc or Isradipine - generic vs brand

Switching back to DynaCirc Cr

The Future of Isradipine and PD

April is Parkinson's Awareness Month
Visit PDF for suggestions of group activities

And if you live in Northeast Ohio

There is a Benefit Recital

for Parkinson's Disease

to be given by Clair Allen, violinist

whose Father passed away earlier this year

following a long battle with PD.

Claire is dedicating her Senior Recital to his honor.

Donations will go to the Michael J Fox Foundation

to support Parkinson's research.

Works by Schumann, Bach, Dvorak and Bartok

Sunday, April 11th, 2010 at 2:00pm

Baldwin-Wallace College
Gamble Auditorium, Kulas Musical Arts Building

To make a donation follow the links at TeamFox.org

Parkinson's Disease: Calcium Channel Blockers with Treatment Potential

2010-04-04T14:02:00.004-04:00

CCBs that cross the Blood Brain Barrier for PD

Most of us read of the California-Denmark study based upon many years of data

from which it was observed that some calcium channel blockers have been found

to decrease the PD risk factor by about 27%.

But what about those who already have Parkinson's?

Today we'll skip the toxic dopamine argument between Mosharov and Surmeier etal

and just take an actual look at the CCBs in the Dihydropyridine class.

Specifically we show the L-type CA(2+) CCBs that can cross the blood brain barrier.

Next we'll post the discussions, the disagreement and study links.

DIHYDROPYRIDINE CALCIUM CHANNEL BLOCKERS	Also known as	Notes
Amlodipine	Norvasc Perivasc, Istin, Agen, Aken Amidipin, Dailyvasc, Lopin, Amcard, Ambolet	Crosses BBB 3rd generation Lipophilic Dihydropyridine May accumulate in brain
Aranidipine	Sapresta	-
Azelnipidine	Calblock	Crosses BBB scavenges hydroxyl radicals but not superxide radicals Reduced levels of intercellular ROS
Barnidipine	HypoCa	-
Benidipine	Coniel	may act in a similar manner to nimodopine
Cilnidipine	Atelec, Cinalong, Siscard, Cilacar	Crosses BBB dual blocker of L & N-type calcium channels does not target protein kinase C
Clevidipine	Cleviprex	Crosses BBB ultra short acting intravenous CA2+ CB
Efonidipine	Landel	Another T-type selective CCB some L-type inhibition
Felodipine	Plendil Renedil (in Canada)	Crosses BBB 2nd generation
Isradipine	DynaCirc, Prescal	Crosses BBB 8 hour half-life 2nd generation
Lacidipine	Motens, Lacipil	Exhibits high partition coefficients into phosphatidycholine
*Lercanidipine*	Zandip	Does not readily cross BBB 3rd generation has a molecular design which imparts greater solubility within the arterial cellular membrane bilayer, membrane-controlled kinetics and a high cholesterol tolerance factor.
Mandipine	Artedil, Calslot, Manyper, Iperten, Mandipot Manivasc, Vascoman	3rd generation less potential for pedal edema than other CCBs
Nicardipine	Cardene, Carden SR	Crosses BBB Similar to Nifedipine 2nd generation
Nifedipine	Adalat, Procardia Apo-Nifed (Canada) Novo-nifedin (Canda) Nu-nifed (Canada	Crosses BBB Lipophilic Dihydropyridine
Nilvadipine	Nivadil	Blocks L-type channels
Nimodipine	Nimotop, NIMO Nimodipina	Crosses BBB similar to Nifedipine Lipophilic Dihydropyridine
Nisoldipine	Baymycard, Sular, Syscor	-
Nitrendipine	Cardif, Baylotensin, Baypress, Deiten, Nidrel, Nitrepin	-
Pranidipine	Acalas	Carries grapefruit juice warning as do other CCBs
DIHYDROPYRIDINE CCBs	Known as	Notes

Differential Diagnoses and Parkinson's Disease

2010-03-29T20:55:00.008-04:00

What do the stereotypes mean for you and PD?

We already know that the precursor symptoms of Parkinson's disease can show their presence years before the disease is full blown and diagnosable. We always want to be reassuring or to be reassured when we notice them. So we tell each other and ourselves:

"Oh, it's nothing"

"You're just stressed"

"Well who wouldn't have sleeping problems, you're depressed"

"Losing your sense of smell is convenient, now you can avoid changing the cat box"

"Perhaps that neck and shoulder pain is from the way you sit at the computer"

"Get another pair of shoes, you're dragging your leg when you walk"

"Get a new pen, your handwriting has changed"

"That tingling is the beginning of carpal tunnel, get a wrist rest"

"Try these pills to help you sleep or for your depression"

"Who wouldn't be depressed, you're not sleeping enough"

And so a few years pass and the next symptoms appear and you make that dreaded appointment. Afraid to know but afraid to delay treatment.

When that tremor appears, people know it is time. The good news for many is that that an action or a postural tremor is not PD. Sometimes it is a sign of Essential Tremor, which isn't curable but in many cases more manageable. And you can drink to that. But that postural tremor which occurs not when the limb is at rest but rather when performing an action can also be a sign of renal or liver failure, of hyperthyroidism, of Dystonia; it can be caused by medications, hypoglycemia or Fragile X Syndrome(FXTAS). The list is long and the diagnosis needs a professional so that the proper treatment can be initiated.

Then there are the people diagnosed with Parkinson's Disease who actually have Parkinson's Plus: the Multiple System Atrophy group (MSA), Progressive Supra-nuclear Palsy (PSP), Dementia with Lewy Bodies (DLB) and Corticobasal Ganglionic Degeneration (CBGD). There is even Parkinson's with ALS The correct diagnosis is necessary to avoid delaying the correct treatment to improve quality of life.

Let's face it, for many people it may seem to be less frightening if they can arm themselves with information before their doctor's appointment. Reading about conditions can actually help you prepare a more thorough list of symptoms. Other people only want to know more after the diagnosis. Before getting any on-line prompts and suggestions, it's a good idea to make that list of all your symptoms and when they occur. That way you won't be as easily swayed by suggestion.
.

Although there is not always good news, there are helpful online sites for many conditions. The Parkinson's sites are listed in the right hand column here as Helpful Links. For Parkinson's Plus one of the most informative sites is actually eMedicine from WebMD. The National Institute of Neurological Disorders and Stroke (NINDS) provides a brief but helpful overview of tremor. So does Medline Plus. You can read about Essential Tremor at several sites. In our opinion the best site for Essential Tremor information is WeMove.org. Another site with a helpful chart of pathology of the nervous system is Wikipedia.

The point is that if you are prepared for your doctor's appointment by having a symptom journal, you can be not only proactive in providing some of the information needed to make the most accurate diagnosis but you can also become a significant part of your medical team. And yes, you are going to need you.

We know of patients who have been told to go home to die. While having your financial affairs in the best order possible and by spending quality time with family and friends is excellent advice for everyone, we just heard a patient's take on that give-up advice from a very courageous woman. When told that there was nothing she could do for her MSA, she asked the doctor if he would give his wife, daughter, mother or sister that same advice. He saw her point and treatment became interactive. We think she's doing very well in finding a course of alternative treatment. She said she had no choice, she wanted to live and there was no hope by following the doctor's advice.

Even if those early warning signs don't send you to the doctor, at least make a mental or written note. If the symptom persists, pay attention, your body is telling you something that could be important.

Finding a Safe Online Pharmacy for Parkinson's Disease Medicine - part I

2010-03-14T22:58:00.014-04:00

What if you can't find the PD medications you need for your treatment at a local pharmacy?

For those of us who were born in a time when information on almost everything was not readily available in our homes, it is amazing to be alive when vast stores of knowledge are finger taps away even when we are in our cars or hiking in the park. When our children were growing, we kept a dictionary in almost every room. A phone interruption at dinner time was not acceptable but stopping to look up the meaning of a word was encouraged.

When I was a child, there was an encyclopedia set to put one on the right track or just to read, page by page for the fun of learning about anything. What do you want to know about Anacondas?

Now there is a huge overload of information. We love that. But not all of it is factual. Some is poorly edited or not accurate; some is sound- byte brief and some is just designed to separate us from our money.

Because UCB has not been able to provide positive news about the Neupro patch availablability in the USA as they wait on the FDA, I thought I would continue the search of online pharmacies to see what I could find out there. I found several online pharmacies which list the patch. I noticed was that the patch is very expensive. Because we had no knowledge of the prior US cost of the patch I decided to compare other medications for which I knew the price. They were expensive...not that expensive but at least 25% higher in price. Of course there is also the question of the cold storage delivery. And that is a BIG question.

We began to receive questions about the availability of other medications. These questions were from markets with which we were not familiar. I just did a check on an L-type CCB, DynaCirc CR, availability and communicated with GlaxoSmithKline (GSK) as part of that search. Turns out that despite the fact that they make the product and have offices in Australia, you can't find DynaCirc in there. You can, however, buy it from an online pharmacy in New Zealand, not to mention Israel, Canada and a few other places where I could not verify the online pharmacy.

I also found an online site which will check for some comparative prices and provide information about the pharmacies. Therefore I did a domain search online because it is important to know the company trail - how long have they been operating their site - are they here today but gone when you are entitled to a refund or didn't receive the product they didn't really mail to you after charging your card.

Since this company has been in business since 2002 with a 2008 update, we're passing that backlink along to you with a warning. Although there are several ways to check for information things at the Pharmacy Checker website be advised, they do not list every bona fide online pharmacy, only their clients, and it is possible that they have some questionable clients on-board or at least did at one time.

This problem means that before you use any online company check the domain and also look for scam warnings. Due Diligence on your part.

Not all scam warnings are valid. Some are just from customers who didn't read the shipping charges or the estimated wait time for arrival. Other complaints are very serious. These complaints includethe company shipping the wrong item and labeling it incorrectly; taking money for the brand and getting a generic which while similar might not be the same. And even worse, counterfeit pills. Other scams include charging your card while not actually shipping the itemor submitting charges without authorization.

Companies can charge for shipping on a regular basis when you did not authorize such a program. Another danger is that you might receive out of date medication.

If your credit card is charged for any fradulent reason, report it to your card company immediately as this will enable to limit your obligation and in some cases your card company can bill back to recover your funds. If you reach this point, you can help others by reporting the scam and company to lots of online scam reporting sites and to any governing authority.

You need a prescription for prescription medication
No prescription required is a red flag!

Another cautionary when ordering from a Canadian pharmacy is to look for the seals of accreditation. Some are real and some are fake. Note the seal and check with the issuer. You can use either of the following links at the Canadian International Pharmacy Association (CIPA) to verify accreditation of the pharmacy you are considering. If you want to verify membership: contact CIPA. They have a similar link under consumer safety. They will also list known sites which display a fake CIPA seal. There are other seals as well. Individual provinces will also require accreditation. As a matter of fact there is also a seal for the

Pharmacy Checker website.

Things to watch for:

Phone and fax numbers. Give them a call on their 800 number ostensibly to verify their mailing address or shipping & handling fees, whatever. But try calling at an off business hour. Did you get a voice mail? Anything? Nothing tells you to move on. Don't leave a phone number or an email address.
Does the site list an address - although this could be a mailbox company which would provide both street number and suite number they should be a legitimate pharmacy with a regular address. I'm not so sure about companies which have drop shipping.
Is their domain check questionable datewise?
The AARP reported Double Drug Sting - just noticed this one - interesting
Do you have online access to the company pharmacist?
Do they ask for the prescription - if they don't - let your fingers walk away
Is the price too low to be believed - don't believe and don't buy!
Have you done your due diligence? Are you dealing with a legitimate company?

We wish that Parkinson's medications were available to all patients everwhere at affordable prices for everyone. But the sad fact is then this isn't the case. So we click our fingers on the keyboard and our options are displayed on the screen before us.

Attention for Young Onset Parkinson's Disease

2010-03-11T23:03:00.006-05:00

There isn't nearly enough discussion of early or young onset PD

Young Onset Parkinson Conference

National Parkinsons Foundation-NPF and the American Parkinson Disease Association, Inc are co-sponsoring the 2nd
Joint Young Onset Parkinson Disease Conference in Sacremento, California. We are all fortunate to be able to join part of the conference from the comfort of our homes on Saturday, March 13, 2010 - 9:00am to 1:15pm Pacific Time and noon to 4:15pm Eastern Standard Time.

All you need to do is to register at the APDA website and tune in at your equivalent time zone start time. Or you can select the sessions you wish to see and join then. So click on the link to go to the American Parkinson Disease Association (APDA) to register for the webcast
Below is the Saturday, March 13th Webcast Agenda
The webcast agenda begins at 9:00 am pacific standard time for us we:ll join at Noon EST

9:00-10:15 am
The Electric Brain: Tailoring DBS Therapy for Parkinson’s Disease Patients
Michael S. Okun, MD
10:45 - 12:00
Complementary Therapies: Expanding your Symptom Management Options
Melanie M Brandabur, MD, MDS
1:30 - 2:45 pm
Update on Gene Therapies for Parkinson’s Disease
Michael J. Aminoff, MD, DSc, FRCP
3:00 pm - 4:15 pm
Parkinson's Disease Treatment: Is Exercise Really Medicine?
Jay Alberts, PhD
We've watched several short videos by Dr Alberts and we're really excited about the chance to hear a longer discussion. It is possible that in addition to the benefits of exercise and specifically of Forced Exercise which has been shown to reduce symptom severity and reduce reliance on medication for up to 4 weeks after cessation, there may be a benefit for neurogenic orthostatic hypotension. We're only speculating on the last but we're hoping to hear that on Saturday.
~~~~~~~~~~~~~~~~~
From Parkinson's Action Network (PAN)

NETPR - Neurotoxin Exposure Treatment Parkinson's Research program received $2.5 million for fiscal year 2010 in the Department of Defense Apropriation bill. This funding is an add- on each year which means that every year an effort must be extended to have it included.
The 2/17/10 16 Annual Research and Public Policy Forum has been archived but is difficult to locate at the PAN website. It is worth watching in segments, however. And as soon as we figure out how to open it, we'll let you know. If you find it first, please let us know.
Friday, March 26th 2010 is the deadline to ask your Senator to support NETPR.

Last week after the PAN webcast we wrote about the need for everyone to do their part to develop a Registry database for PD and MS that can drawn from current sources. Everyone benefits.. From the Parkinson's Action Network comes the update on the support for the National MS and Parkinson's Disease Registry.

The Importance of Advocacy
If you need a better understanding of what it is the PAN really does and why it is so important, watch the PAN Advocacy video
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Because there are few groups for a sister disease, MSA, and less research, we thought that we should mention this news From Facebook:
Although unofficial, Miracles for MSA (Multiple System Atrophy) has asked that we observe March as MSA month. Since some people have probably been misdiagnosed with Parkinson's disease with a rapid progression when in fact they may very well have MSA, it is only fitting that we should respect and honor that wish.
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I'm sorry to say that there is still no news on the Neupro Rotigotine Transdermal Patch horizon. We'll post as soon as there is some positive news about its return to the US. There are Canadian sites where it can be ordered. We've done a bit of shopping online and the prices are high. We're working on that article and will try to get it posted in a few days.
~~~~~~~~~~~~~~~~~~~
For those who are experiencing Neurogenic Orthostatic Hypostension as a symptom of PD or medications or MSA as a result of deficient release of norepinephrine, Droxidopa from Chelsea Therapeutics while available in Japan is still in Phase III clinical trials. We have learned that for MSA patients it can be made available on an emergency hardship basis through your physician.
We'll be writing more as it is closer to being approved by the FDA.

We're enjoying the pseudo March Spring before the next onslaught of midwest snow.

The dogs waited patiently for hours below a tree for the squirrels to come down to play. No fools, the squirrels did not descend to that level.

The Time Has Come for A National Registry for Parkinson's Disease

2010-02-21T20:45:00.010-05:00

Our Armchair Attendance at the 2010 Parkinson's Action Network (PAN) Forum

A few days ago we signed in to "attend" the 16th annual PAN Research and Public Policy Forum in Sunnyvale, CA without having to venture into the midwest cold. We stayed from beginning to end, no mean feat when one of us has PD. We really like webcasts because they provide us with the ability to interact while not having to say "excuse me/pardon me" when it's time for a pit stop.

Although we have written about some of the covered topics in recent months, we'd like to mention one very important issue: data analysis of neurodegenerative conditions because it is an area where we all can have a voice. The Parkinson's Action Network is our advocacy voice but without our support in return, that voice will not be nearly as loud.

Important legislation is in committee and in order for the best interests of people with Parkinson's to be represented, it is important that your Congressmen and women and your Senators to be encouraged to co-sponsor HB-1362, the National MS and Parkinson's Disease Registries Act. The Senate equivalent bill is S-1273.
Without the statistics generated by such a registry, which will draw from a number of resources, target areas cannot be identified, the need for certain research dollars are hard to justify, better data for research and treatment can be delayed.
Currently we do not have a accurate information regarding the incidence and prevalence of PD and other neirodegenerative diseases. These statistics are necessary when planning programs and services, advocating, and focusing research for risk factors, genetics, environmental exposure, changes in incidence/prevalence/distribution. Earlier studies did not have the higher proportion of older Americans in the mix and most certainly did not have the incidence figures for Young or Early Onset Parkinson's (YOPD).
The National Registry will draw securely from a broad source of available information in order to compile the requisite information. While there are two states which do have the records and provide good models, what is needed is a national picture.
To lend your support for HR-1362 you can click here to link to the PAN prepared letter site.
You will then prepare your email message
Simply type in your zip code, the proper representatives' email address(es) will appear - depending on the district - you may have to add your home address.
Do not forget to enter your email address if you will be sending through the PAN system. If you are mailing the letter, it may not be necessary
You can then use the letter template
ADD your personal story or message if possible because it carries more weight.
Write your additions to the letter in 5 minutes or less - okay, it might take longer but not that long - I just did mine. The system will indicate if your legislator has already co-sponsored the bill and will generate a thank you letter - be sure to send that.
Otherwise send the request for co-sponsoring letter with your personal revisions or additions
To send a message to your senator requesting support for S.1273 - yes, separate letters are needed, click here.

I've sent mine and Steve will be sending his soon. I hope that you will join us.

Just a reminder from the PAN forum, if you're written to your legislators before and they had responded positively, be sure to thank them. When you're bombarded by requests, problems and complaints, it is nice to read a kind word.

We'll be back with more information from the forum. But just in case you'd like to view it, you can do so by going to the Parkinson's Action Network website. I'm not sure if it is posted yet but if it doesn't, just bookmark it and return in a few days.

To follow these both the Senate and the House bills

Senate Bill: S.1273 National MS and Parkinson's Disease Registries Act

House of Representatives bill: HR1362 and here

The next webcast of Parkinson's disease interest is from the Parkinson's Disease Foundation and this event will be held on Tuesday, February 23, 2010 at 1:00 pm EST. The topic is Nutrition and Parkinson's Disease.

You can link to the PDF website for webcast access here.

PAN is also working to Extend Exceptions to Medicare Therapy gaps.

What is Parkinson's Disease?

2010-02-14T16:30:00.008-05:00

PD Basics

Medically

Parkinson's disease is a chronic, progressive neurodegenerative disease - meaning, according to the CDC, that it will last longer than 3 months or in this case until death do us part.

It has the 2nd highest number of neurodegenerative disease patients; only Alzheimer's is higher. It is estimated that there are almost 1.5 million people who have PD in the US alone and more than 5.5 million globally. The numbers point to more men than women developing PD and to more whites with PD than Black Americans of African ancestory, Africans or Asians.

Parkinson's is classified as a motion disorder and is treated by specialists in movement disorders. The original diagnosis should be made by a neurology specialist. There is also a significant number of non-movement symptoms as well; and some of the precursor symptoms are not motion related.

A rose by any other name

Parkinson's disease has been called many things. Paralysis Agitans has been called a disease of old age. While younger people can develop it and do, it more commonly develops in late middle age with the odds increasing every 10 years of age up to 89.

It has been called a disease of sleep disorder and of depression. Of course everyone knows its modern history when it was called "the shaking palsy" by James Parkinson in 1817 and subsequently named after him a few decades later by Jean Martin Charcot who also studied the condition.

Parkinson's has also been called a prion disorder by Dr Stanley Prusiner because of the alpha synuclein pathology.

Historically

The disease has been known for centuries. PD has a documented history dating back about 5,000 years in India where it was known in Ayruvedic medicine as Kampvata (severe body shivers). 2,500 years later its symptoms and treatment were described in China. A specific genetic line has been followed from China to the US. The disease appears to have been identified in Greece in around 800 BC and certainly by 310 BC it was known and studied. It was described in Rome about 2,000 years ago. It was later described by the Greek physician, Galen, about 1,800 years ago.

How will I know?

The disease begins to manifest early in many people with seemingly unrelated symptoms such as diminished sense of smell (partial usually), depression, sleep disorders, foot or leg drag and lack of arm swing when walking. In some people it can manifest as smaller handwriting (microphagia) and in women as pain in the neck or shoulders. About 75% of people with PD begin to have tingling or tremors in the extremities on one side of the body as a symptom which eventually sends them to the doctor for a diagnosis.

The tremors and actually most of the above precursor symptoms manifest because of chemical imbalances in the brain. Parkinson's is usually diagnosed after the death of about 60-80% of the dopamine neurons in the substantia nigra pars compacta of the basal ganglia. But before PD can actually develop a significant number of norepinephrine neurons must die also. As a precursor of norepinephrine, dopamine is the target area for PD treatment.

The predominant motor symptoms are defined by the acronym TRAP. Tremors, Rigidity, Akinesia (Bradykinesia) and Postural Instability all movement related.

What's Going On?

Essentially it is the lack of balance or homeostasis between acetylcholine (which is in its normal abundant state) acting as an excitatory neurotransmitter and the diminishing supplies of the primary monoamine transporters dopamine, norepinephrine and serotonin, which serve as a message inhibitor. In other words the acetylcholine instructs the muscle to act or tense up while the dopamine sends the message to relax.
When the relax message cannot be sent as often, the rigidity and stiffness, the tremors and dyskinesias which typify PD, are seen. The stiffness can result in cramping and a little discussed symptom of Parkinson's known as pain. Usually treating the symptoms will relieve some of the physical pain.

Although the norepinephrine tries to take up some of the slack, there are fewer norepinephrine neurons in the brain to begin with and so with fewer precursor cells to make it, it too has been degenerating.

The why of dopamine cell death is being researched now and although there are some differences of opinion, it is thought that the cells die possibly when excess calcium in the cell causes the dopamine to leave the vesicle too early to be used and by hanging around in the cytosol it combines with alpha synuclein to become a gummy mess and ultimately die. Dopamine continues to die throughout the course of Parkinson's disease.

It's not all in the family

The disease is not contagious and at this point has only been identified as being about 15% or at most 20% genetic. Because there are several genes which have proteins mutations (doubled or triples) associated with PD and because they are each more common to specific geographic areas for specific gene lines although there are almost certainly trade route connections and migration or emigration patterns.

Despite the genetic research for PD, it is still called an idiopathic disease because the primary cause is unknown. There is YOPD, young onset PD and Juvenile Parkinson's both of which are felt to be predominantly genetic in origin.There are also other categories such as LBD or Lewy Body disorder which can occur before Parkinson's with parkinsonian symptoms developing later as well as PDD, Parkinson's disease with dementia in which the PD occurs first.

Even the genetic cases in older adults appear to have an environmental trigger. Parkinson's symptoms can also be drug induced. Other triggers include severe head trauma, certain heavy metal exposure, certain chemical exposure. It is difficult to establish if stress is an early contributor or a body reaction to the subtle loss of homeostasis.

When the cause is genetic, Parkinson's can be autosomal dominant or autosomal recessive. There is no reason to cast blame as the genes can be hiding in the woodwork just waiting as the disease can skip generations.

We Are the World

There are other areas of the world which appear to have a lower incidence of Parkinson's disease. That may be due to a few different reasons, however, there are places where there is a high prevalence due to oddities of diet which cause parkinsonism if not PD.

PwPs around the world are generous in sharing their experiences with others. Support groups abound and fund raising never stops because so much funding is needed to support research for better treatments and cures.

There are signs everywhere

Parkinson's is also known as primary parkinsonism because it appears to be a collection of symptoms which manifest in different ways and combinations in different people. Parkinson's is a disease which can cause any combination of the symptoms.

Tremors, slowness of movement (bradykinesia), stiffness and rigidity, swallowing and choking issues, change of voice, lack of facial expression, dyskinesia and dystonia (especially as a medication side effect) leg drag, lack of arm swing, urinary issues (such as incontinence, urinary frequency and urinary hesitancy) constipation, erectile dysfunction, dental problems, vision issues, loss of sense of smell, depression and apathy, hallucinations (usually a side effect of medications) dementia, cognition issues, drooling, breathing problems, postural instability, parkinsonian gait, freezing of motion, microphagia, change of skin condition (dry, oily) and the list goes on.

Symptoms and disease progression of the disease result in the inability of the patient to perform tasks of daily living and eventually unable to feed themselves or eat. The end stage symptoms can require feeding tubes and nursing homes.

One unusual feature of the disease is that many of the physical symptoms begin on one side of the body only, unilaterally. Tremors are usually resting tremors, meaning that the person is not initiating an action. As the disease progresses, the symptoms begin to appear bilaterally.

Can we make a difference?

Certain treatments can delay the progression of the disease. Slowing the progression of all PD cases is crucial. Some people have a slower progression of the disease than others but until there is a cure, the slower the progression, the better the quality of life. Other medications target specific symptom relief via dopaminergic action.

What Parkinson's becomes is an insidious disease which can steal normal body function from people and replace it with huge expenses, create additional family stress and adjustment, subject people to public ignorance and ridicule. It is also amazing to know that it is a disease with a surprisingly low suicide rate, surprising when you consider that at least 40% of PwPs have PD depression. But it is also a disease of hope.

Although current medications and therapies help to relieve symptoms or slow progression, different people respond in different ways and much attention to detail is required by both patients and physicians. Patients and their caregivers learn to be their own best advocates, with special thanks to the printers attached to their computers.

Is there light at the end of this long tunnel?

There is much ongoing research by some of the best scientific minds in the world. At least one medication in the pipeline shows serious promise. More is being learned everyday as scientists worldwide are exploring and sharing small and large aspects of the causes, treatment targets, improvement of existing treatments. While the cure may be years or a couple of decades away, the body of knowledge is increasing and with it the hope that when the cure(s) are found that the regulatory bodies will fast track them for the people who have lived with hope for so long.

Parkinson's Disease Events for Winter-Spring 2010

2010-02-05T16:09:00.007-05:00

You can take part in these PD events in a variety of ways: by donation, in person, at home, on-line and by phone.

We talk, we read, we share - here are some events where we can join together.

PAN Forum on February 17, 2010

On February 17 from 11 a.m. to 5 p.m. EST

Parkinson's Action Network (PAN) will host a live, online broadcast featuring presenters

who will discuss the latest in Parkinson's disease research and policy

Pan Forum Registration

Additional information will be made available after registration

April is for Parkinson's Awareness while the tulips bloom

Parkinson's Awareness Month - April 2010 - US and Canada

and

Parkinson Society Canada

Parkinson's Awareness Week UK April 20-26th 2010

Parkinson's Disease Society

World Parkinson's Day April 11th 2010

EPDA

PD Expert Briefings
Tuesday February 23, 2010 1:00pm EST
length: 1 hour
Nutrition and Parkinson's Disease
led by Christine C. Tangney, Ph.D., F.A.C.N., C.N.S
Associate Professor, Clinical Nutrition
College of Health Sciences, Rush University Medical Center

Coming events sponsored by the Parkinson's Disease Foundation:
What's in the Parkinson's Pipeline?
Tuesday April 20th 1:00 pm ET
David G Standaert, PH, PhD
John and Juanelle Strain, Professor and Vice Chair of Neurology
University of Alabama
Sleep Disorders and Parkinson's Disease
Tuesday, June 1 1:00pm ET
Joseph Friedman, MD, Clinical Professor of Neurology
Brown University

From the National Parkinson Foundation

Young Onset Parkinsons Conference March 12-13, 2010 in Sacremento, CA

Parkinson's Disease Walks scheduled for 2010

The Parkinson's Unity Walk

Parkinson's Unity Walk 2010

Sunday April 24th 2010

New York, NY

The American Parkinson Disease Association, Inc

Schedule of Parkinson Walks for 2010

Parkinson's, a Disease of Shortages

2010-01-28T19:31:00.006-05:00

Help to find Sinemet, Plus and Sinemet CR for PD during the current shortage

Everywhere we look we can read that PD is a chronic progressive neurodegenerative disease which manifests because of a shortage of dopamine neurons in the brain thus causing no shortage of motor and non-motor symptoms. So shortage is no stranger to the Parkinson's disease patient and we've talked about many of those for months.

We haven't talked from personal experience about levodopa-carbidopa (Sinemet) as a symptom relief treatment for Parkinson's disease. About 8 weeks ago Steve began taking levodopa-carbidopa. He is actually on a fairly low dose which seems to help a great deal with stiffness, a bit with tremor and not so much with weakness but he still hasn't titrated up to the full prescribed dosage - we're on hold for a totally different reason because we don't want to.

What we have seen is that you can set the clock by the wearing off because he immediately asks if he is due for any medication even waking from a sound sleep. But there are no side effects other than feeling somewhat drowsy.

It was his idea to take levodopa-carbidopa and his neurologist agreed to write the prescription. He has not reached the point where he needs a higher dose to be effective and so he has no reason to take the controlled release (CR) form for a steady, continuous delivery. And because the first morning dose of the timed-release pills may actually take much longer to start working, we hope that we will be able to control the stiffness with the generic version.

Many people who require the steady release over 4 to 6 hours and many of these people will be affected by the shortages of:

Sinemet tablet 12.5/100 mg
Sinemet CR tablet 50/200 mg
Sinemet Plus tablet 25/100 mg

These product shortages were announced by Bristol-Myers Squibb Pharmaceuticals Ltd in August 2009 and by Merck Sharp & Dohme Limited (MSD) in October 2009. The shortages are expected to last from 2010 through 2011. If you're not sure it your pill is on the list, you can check the European Parkinson's Disease Association chart.

The product distributor, Bristol-Myers Squibb indicated in an August announcement that there were packaging issues which would cause a three week delay.

Also announcing a shortage was Apotex, Inc for the generic Apo-Levocarb CR (200/50) available in Canada but now discontinued. Patients are encouraged to consult their doctors for treatment alternatives. Bristol-Myer Squibb is the distributor for Merck, supplying to Apotex. When announcing in Canada, no reason was provided, however other reports suggest that consumer stock-piling was already in progress creating a short supply.

The good news is that many generic versions, usually slightly weaker, still appear to be readily available, so it is not time to panic if you are using the medication for Parkinson's disease, parkinsonism, encephalitis caused parkinsonian symptoms, carbon monoxide or manganese poisoning. Just how long this will last is unknown.

Merck has explained that the issue is not one of safety but rather a change in the supply source and the time frame required for proper jurisdictional approvals. Because of contractual obligations, some markets may fair better than others. Because of the length of time for regulatory approval, the wait time is uncertain.

People who are already taking Sinemet CR, Sinemet Plus of Sinemet 12.5/100 and are concerned about not being able to renew a prescription can call one of several numbers worldwide to speak to the customer relations department at Bristol-Myers Squibb Pharmaceuticals Ltd (800) 332-2056 or at Merck Sharp &amp Dohme Ltd or the parent company Merck & Co, Inc.

The following countries have offices which you can contact at the Merck links above:

Argentina, Australia, Austria, Bahrain, Brazil, Canada, Chile, China, Columbia, Costa Rica, Croatia, Denmark, Ecuador, Egypt, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Iceland (see: Denmark), India, Indonesia, Ireland, Israel, Italy, Japan Korea, Kuwait, Latvia, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Oman, Pakistan, Philippines, Poland, Portugal, Qatar, Romania, Russia, Saudi Arabia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, UK, United States, Venezuela, Vietnam.

If you live in the UK, you can make sure that your physician has the following number:+44(0)1992 467272.

Thus far we have not seen warning for the other L-dopa/carbidopa combination medications.

Just a few reminders in case you are having an issue locating a supply:

You can not split a timed release tablet
You could have a withdrawal problem if you simply stop taking the medication; consult your physician about a lower dosage prescription in order to titrate down.

And if this isn't bad enough, there is also going to be a shortage of Eggos until mid-2010 due to flooding at the Atlanta bakery in October, 2009.
~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
Addendum
Per information from the American Society of Health-System Pharmacists"

Back on February 23, 2010, GlaxoSmithKline (GSK) had acquired Reliant and announced that DynaCirc CR had been unavailable during the transition period. The 5mg and 10mg pills are available now.

Activis Group did make some changes in isradipine packaging. The 2.5 mg 100 count package is no loonger but the 60 count is available to pharmacies. The same is true of the 100 count 5mg package. Now only 60 count packages are available.

Watson Pharmaceuticals, which was formerly Cobalt, has isradipine available in 2.5 mg and 5 mg 100 capsule counts.

For those who have been taking the CCB Nimodipine, that shortage has been resolved.

Titration and Parkinson's Disease Medications

2010-01-25T12:25:00.006-05:00

Withdrawal happens - it is not punishment for taking bad drugs

Loosely related ramblings

There are several types of medication which require a low, steady buildup to the necessary effective dosage. You doctor advises you, the pamphlet you get from the pharmacy will tell you and so will the online sites for that drug. Sometimes in our hurry to switch from one medication to another, it is easy to forget that if you go up slowly, you need to titrate down in a similar manner in order for your body to adjust. And that even if you don't, your body has built up if not a dependence, at least a familiarity with the medication that requires recognition.

While titration downward may cause some symptomatic issues, in the long run your body will thank you. There can be some serious conditions resulting from an abrupt withdrawal. Titrating down from any medication you are discontinuing may be a general rule of thumb until more research is conducted. But there is sufficient research on many meds.

A few weeks one of Steve's doctor prescribed a medication with which I was not familiar. Actually I didn't understand the name he said on the phone and figured I'd just look it up once I had the bottle in hand. (Let that be a lesson to me about being intimidated by an impatient doctor.)

Once home from the pharmacy I began the online search and discovered that this medication could not be taken within 14 days of having an MAOI in the system. So this was not the medication for Steve because he was not giving up the Azilect (an MAO-B inhibitor) which he has been taking since soon after it hit the US market. Although this is a new doctor for Steve, I had provided him with a written list of all meds and regular supplements as well as all symptoms and current issues but he just missed this call. It is important to do your own homework.

A longer time ago than I care to realize, we switched our son from a pediatric to an adult medicine doctor because the peds doc and I weren't in sync. We disagreed too often for either of us to be comfortable. And the worst thing is that I was right far too often. I cite the last incident as an example.

It turned out that a sad prior experience shared with me by our beloved Veterinarian over a distemper puppy from the pound. What we learned about pediatric medicine taught us both about how rapidly respiratory issues can turn on you.

In this case I felt that a sudden temperature shift had turned on my son and I wanted his meds switched immediately. The peds doc disagreed. So off we went to Xray. Brought the pictures back to the nurse and we waited and waited in the room designated for such things while the doc read the Xrays and wrote a new prescription because that was what the Xrays told him was needed. Being right didn't help because the peds doc acknowledged it in a surprising way. He left an anxious mother cooling her heals while a very sick child lay on the bench struggling to breathe and with a rising temp for a very long time. Ostensibly the doc was studying and considering while we waited for him to tell us what he had seen and what could be done.

Instead of meeting with us personally, he actually left the building for lunch. He'd told me off earlier so rather than face me, he made tracks. Finally I ventured through that closed door through which one is not supposed to travel unless invited, found the nurse and was handed the new prescription with no other explanation. And our son, of course, got better.

There are a few points to that story. Be proactive - Don't sit and wait. You or your family member are your only patient, the doctor has plenty. Only you can get things moving. Don't just sit there.

But the story doesn't stopped there. I moved our son to adult medicine and shortly thereafter took him in as a followup. He came out with a prescription for prednisone.

Anyway here was this young boy who had been prescribed a heavy-duty medication and a few weeks later I realized that the bottle was still fairly full - too full. I asked him about it when he returned from school. He said the doctor had told him that he had to ease his way up - take the medication - and ease his way down. So he had titrated up, didn't like the way the steroid made him feel and promptly titrated his way back down.

Just so you know, why didn't I know about what the doc had told him...because at the first appointment this favorite human doctor had gently closed the door in my face saying, "Mom, this isn't Peds - this is adult medicine and you aren't invited." Although I never regretted that move as it served our son well, it did teach me many years later, that when its PD, I want to be in the room. (And to make sure that Steve has signed the necessary release for me to discuss issues with his doctors.)

So that was how I learned about titration. From our pre-teen son.

Ken in England, who sends us links of interest, recently sent us one about DAWS. Dopamine Agonist Withdrawal Syndrome.

Steve reports that when he discontinued the Mirapex, he told his doctor that he was going to titrate down and his doctor told him how to do it. He reports that you should be able to tell if you are titrating down too rapidly; that if you are cutting back to fast your body should respond. Steve was discontinuing Mirapex (a dopamine agonist) and Selegiline (an MAO-B inhibitor) because he had problems with impulse control disorders (ICDs) and hallucinations as serious side effects of the medications. In Steve's case he was not taking levodopa because that was not his first drug of choice and the Mirapex and Selegiline were working well in controlling symptoms.

Reducing dosage of Parkinson's drugs can cause symptoms similar to those of cocaine withdrawal was a study by Dr Melissa Nirenberg and Christina Rabinak at New York-Presbyterian Hospital- Weill Cornell Medical center NY, NY. What is interesting about this study is that it not only focused only on the ICDs, such as shopping, gambling, eating, hyper-sexuality or sexual behaviors, but also focused on levodopa with the implication that there could be an addictive relationship because of the reward implication of the mesocorticolimbic pathways.

The withdrawal symptoms can be diarrhea, dizziness, anxiety, irritability, agitation, chills. Withdrawal symptoms usually abate but they can be confused with other medical or psychiatric causes.

Dopamine Agonists are not the only meds to watch if discontinuing. SSRIs, Selective Serotonin Re-uptake Inhibitors used as antidepressants to treat depression can do exactly the same thing. And, because they can induce more profound detrimental side effects in a Parkinson's patient, are often discontinued. Caution must be taken when titrating down. You should read more about Discontinuation Syndrome is you plan to discontinue your SSRI.

PwPs may have other medical conditions being treated concurrently. It is important to be aware of all interactions so that adverse affects can be monitored and discontinuation done properly.

There is actually a serious life-threatening condition known as Neuroleptic Malignant Syndrome which can result at both the onset of adding a new drug or the abrupt cessation of certain prescription medications. Making proper titration up and down all the more important.

Withdrawal symptoms are not punishment for people who do illegal drugs, they can happen to anyone.

Additional reading:

A good explanation for the study can be found in another study. Dopamine agonists influence learning and striatal reward prediction errors in PD patients with compulsive disorders

Researchers Identify, Define Dopamine Agonist Withdrawal Syndrome

addendum 4/02/11 A recent study which is now recruiting: Naltrexone for Impulse Control Disorders in Parkinson's disease

Urate: Too Much of a Good Thing or Just Right for Parkinson's Disease?

2010-01-20T19:30:00.002-05:00

PD, MS and Urate: Is there a future?

We've been trying to write a post about urate, a water soluble antioxidant, and Parkinson's Disease for months now but every time we begin we have visions a great uncle whose gout pain was so bad that he had a 2nd accelerator pedal for his left foot installed for his annual cross country drives to Phoenix, Arizona. How could we write about the relationship of low and high urate levels to PD when there was also a real risk from high levels?

So to get gout off the mind we learned from Johns Hopkins that a malfunctioning gene, ABCG2 appears to be the cause of the high concentrations of serum urate which crystallizes in body tissues within joints. The result of course is inflammation and pain. The process occurs when ABCG2 doesn't make the protein needed to move the urate from the kidneys and down the drain. While not everyone with a high urate concentration develops gout, it is a decided risk factor.

Normally present in the blood and spinal fluid, urate, is a salt derived from uric acid. So why should a high level of urate crystals - and there are many forms of these crystals which can build up in tissue as well as in joints - delay or slow the progression of PD especially in younger men? What appears to happen is that those men with the highest level have the slowest progression and are usually losing the fewest dopamine producing neurons. But why?

According to the Harvard two-year study of male patients in early stage Parkinson's disease, those with the lowest progression had higher levels of urate. It appears that their bodies can metabolize the urate so that it is effective rather than destructive. The result is that fewer dopamine neurons appear to be lost.

Another discovery was that the higher the urate levels, the slower the cognitive decline.

This doesn't mean if you have Parkinson's or Multiple Sclerosis that you should run out to a body building store to buy inosine, the antioxidant precursor to urate. The levels may stem from dietary intake and the proclivities of the individual body to metabolize urate. It would appear far wiser to wait for Dr Michael Schwarzschild, MD, PhD director Molecular Neurobiology Laboratory Massachusetts General Hospital and Dr Alberto Ascherio, Harvard School of Public Health and Harvard Medical School, Boston, MA and teaming with the Parkinson's Study Group of US and Canada to take their studies farther with the support of the Michael J Fox Foundation. Currently SURE-PD (Safety of Urate Elevation in PD) is in phase II clinical trials testing inosine efficacy and safety.

There is, however, a flip side to urate. Normally functioning as an antioxidant, in certain circumstances it can become pro-oxidative. However, ascorbic acid may prevent the prooxidant effects.

There are gout studies which show that intact skim milk might have a urate lowering effect while the control soy milk showed a serum urate increase. Which means we're back to those peculiarities of body chemistry: Parkinson's and higher levels of urate with slower progression while at the same time higher levels of urate are also associated with gout which in turn is associated with a higher risk of diabetes, cardiovascular and chronic pulmonary disease, hypertension, hyperlipidemia and kidney stones to name a few.

What else do we know about urate? We know that uric acid is associated with iron binding properties. Hmm. We know that it is possible to make dietary adjustments to increase plasma urate levels but we don't know whether there will be additional risks of gout or other conditions. A 2008 discovery, thanks to genome-wide association scanning, has been that variations of the SLC249 gene appear more often in those with high serum urate than those with in normal levels. And we know that by increasing dietary intake of fructose and purines the urate levels will rise.

So we await the results of ongoing research which may prove beneficial to men with Young or Early Onset Parkinson's as well as those in the early stage of PD. Because PD treatments are either symptomatic, which may or may not be effective, or neuroprotective, which appears to hold more promise but is less common, we will be very interested in the progress of the SURE-PD trials.

Dehydration and Parkinson's Disease

2010-01-04T17:25:00.011-05:00

It's so easy to confuse PD symptom side effects with dehydration

You don't have to be in a desert, the middle of the ocean, an athlete in training or even a gardner pottering around under a hot summer sun to suffer from dehydration. Dehydration is always a risk of disease and aging. For a Parkinson's disease patient it is very easy to misread symptoms of dehydration. Dehydration is an urgent condition.

We've talked about the effects of weight loss on PwPs and some of the causes and effects in previous posts. There is no question that improper diet and medications can also cause constipation. In all of these posts we have touched upon dehydration. Now it is time to get serious about the effects of dehydration, the symptoms, why they are easily overlooked in PD and why dehydration must be treated immediately.

Water is 75% of our body weight. Wrestlers, dieters and models know this fact when they need to drop a few pounds quickly to make weight class. In the body it really is "water water everywhere". Water in the cells, the blood and in the spaces between the cells. And that is what Mother Nature intended.

It is easy to forget that a significant amount of water is lost every day when we breathe it out with every exhale, when we sweat and lose more water, when we urinate or move our bowels even more water is gone. This lost water has to be replaced to avoid kidney damage or failure, cardiac problems, coma caused by reduced blood flow to the brain, and death as a worst case scenario. Along the way there can be some very unpleasant problems.

Body chemistry is in constant flux and requires balancing to maintain homeostasis. Parkinson's Disease is all about the loss of balance in so many areas. Prompt treatment is the best possible way to approach restoration of balance. Dehydration is no exception. It is crucial to avoid the effects of the loss of fluid balance as dehydration can acerbate existing Parkinson's symptoms and take you to a very bad place.

When concerned about urinary frequency, many people with Parkinson's simply stop drinking enough. There are Depends for that - not drinking is not an acceptable option.

Swallowing problems create another reason for fluid avoidance because of the fear of choking.

Medication side effects can also contribute to to loss of interest in eating and drinking. Another medication side effect is nausea (leading to vomiting) and diarrhea which deplete even more body fluids.

The problem is that when a PD patient stops drinking for whatever reason, additional damage is done to the kidney and bladder, to the circulatory system as heart rhythm is affected , to the GI tract as constipation is made worse and the cycle feeds upon itself.

Many patients can't tell you or won't tell you that they aren't drinking enough. PwPs are so prone to depression or apathy that they just can't. So when symptoms are noticed, it is time to look for more clues so that you can take action.

Some of the warning signs of dehydration are:

Dry Mouth, Lips and Nasal Passages (can also be a side effect of the meds)
Lack of Tears (and there are other reasons in PD)
Muscle Cramps (always suspect fluid loss, potassium imbalance)
Nausea leading to Vomiting
Lightheadness - Syncope - Dizziness (can occur for several reasons)
Blood pressure changes (both high and low can occur)
Heart palpitations
Feeling too warm (may also indicate fever)
Lack of sweating
Confusion (is not just meds, disease progression, or lack of sleep)
Weakness (another sign of low potassium levels)
Tiredness
Lack of skin elasticity (a common and rapid symptom in the elderly)
Changes in behavior and mood - irritability
Darker colored or strong smelling urine (concentrated urine)
Headaches
even Allergy symptoms.

Although dehydration can cause dizziness which we often see as lower blood pressure, blood pressure may of necessity rise as fluid levels drop. Hyoptension or hypertension can occur and can create additional problems

Electrolyte homeostasis is effected. These electricity conducting salts are found throughout the body in fluids, blood and skin and muscles. Sodium, potassium and calcium are the salts most commonly out of balance in dehydration but chloride, magnesium and carbonate can also be affected. We know how important electrical conductivity is for PD and how delicate that balance can be. Electrolyte balances can be checked through blood tests ordered by your physician.

At the doctor's appointment when dehydration is suspected, blood pressure will also be checked, temperature taken, urinalysis performed If the problem is too extreme or if swallowing is a serious issue, it may be necessary for IV fluid administration.

While waiting for that appointment, it is time to make sure that the fluid levels are gradually increased. Water is most important, ice chips, fruit juice, sports drinks designed to restore electrolyte balance, soups or broth, popsicles are fun and easy; jello has a high water content. Since tea and coffee act as diuretics, they should not be included. You can go online to find herbal remedies which might help to increase thirst as well.

When there are swallowing problems which prevent drinking, do not postpone the home vocal exercises, but also consider getting speech therapy. In addition to exercise, address the eating and drinking issues associated with PD and consider the need to purchase drinking utensils which will facilitate holding a cup that doesn't spill.

Dehydration can sneak past a caregiver just as easily as it can the patient. If you notice changes, are aware of water left in the glass or consistent lack of thirst, it is time to rehydrate. Don't wait - Drink up.

An observation:
In the dehydration process, there seems to be a connection between not drinking enough and not feeling thirsty.
As a caregiver you may find resistance in your patient because they do not perceive what you actually can see, that they simply don't have a sufficient fluid intake.
As a patient, the less you drink, the less thorsty you feel and you need to help your body...your self...by supplying it with the necessary fluids so that you do not become sicker.
It does not take long for confusion and disorientation to appear, not to mention many of the symptoms listed above.

On a personal note:
Our beloved Harry, the Lab mix, became quite sick a couple of months ago. I knew he was sick but the diarrhea (which I addressed immediately) didn't immediately signal me to check his skin resiliency and then the alarm went off. He who normally drinks like a horse, had stopped. I realized it when I didn't have to add a quart of water to the cat fountain a couple of times a day.
A pinch of his skin prompted me to whip out some chicken rice soup which he loves. I kept diluting it but he didn't care, it was wonderfully flavored "people food" and he drank and drank...not all at once but gradually. He went through a half gallon over two days before he began drinking from his water dish and the fountain.

On an informative note: Apparently the chicken soup had a good electrolyte balance for Harry. Had he been a human child, he would have been on Pedialyte or an electrolyte drink such as Gatorade. Or I would have made a drink for him using the following formulation:

1/2 teaspoon salt
6 level teaspoons sugar
1 quart (1 liter) drinking water

Change the formula above and you can actually do more damage than good. For an adult daily fluid intake you should multiply that by 2 or 3. I suggest dedicating one ice cube tray (if you have any) and using at least 1 quart or more to make ice cubes. We have found that Steve prefers very cold drinks when we feel his fluid intake is dropping.

Addendum: Steve suffered another bout of stress induced dehydration in late July of 2011. We caught it early but he relapsed and we are still working through those issues.

Parkinson's disease Updates for Cogane, Neupro Patch, Droxidopa, Lu 02-750, and Azilect

2009-12-23T20:51:00.013-05:00

In the news and demonstrating the need for a PD pipeline fast track through the FDA

As of 12/09/2009 Phytopharm has raised the money needed to bring Cogane to Phase II trial in the first half of 2010. The results for the Phase II trial of Cogane, the neurotropic factor which uses both GDNF and BDNF to cross the blood brain barrier, are expected in 2012.

Another announcement is that Cogane will be tested for Huntington's Disease.

Phytopharm stock is doing well.

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For all awaiting the return of the Neupro Transdermal Patch, here's the latest news from UCB, the global biopharma. After the crystalization recall and subsequent removal from both the European and the US market, many patients who had found relief from this unique molecule which helped patients improve against a broad range of day-night symptoms by maintaining a constant plasma level to relieve motor symptoms, sleep problems and morning akinesia (limited motion) were with only enough supply to titrate down.

The patch was approved by the EMEA (the European Medicines Agency) for approval to return to the European market by the summer of 2009 and there are 33,000 PD and RLS patients who are using it in Europe; however, the Neupro rotigotine patch is still not available in the US.

A year ago in December 2008, UCB submitted their response letter to the FDA.

In June of 2009 am extensive update on the cold chain data was submitted to the FDA.

The dialogue continues and it is expected that Neupro will be made available to US patients in 2010 according to UCB.

We've supplied a link to one online pharmacy which will fill a prescription request and other readers have supplied links to others in the comments sections of previous posts. If you're looking for the Neupro patch, check these posts and their comments sections.

June 2010 Neupro Patch Update:
With the blessing of the FDA, UCB has gone back to the drawing board with the Neupro patch to eliminate the need for cold storage. The implication of this announcement suggests that it could be as long as 3 years before the patch can be returned to the USA market.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

In the research and the pipeline are other GDNF delivery options. One approach is biodegradable microspheres still in research. Another is an intranasal delivery in research now studying nasal toxicity and the quantity of the GDNF which reaches the brain. Ths latter study is still in lab rat mode before moving on to human trials.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

The mixed bag news is that there is motivation to develop new therapies which work better than older, existing therapies. That's good. In Europe alone, PD accounted for a $1 billion market which is expected to grow to about $2.25 billion by 2015. Even if a cure is found, there is a growing number of people developing Parkinson's disease as the world population continues to expand and as diagnoses become more accurate (another market in itself) and are done at an earlier stage of the disease...

We'd love to be able to tell you more about a unique dopaminergic agonist being developed but Lu 02-750 is very hush-hush.

In October of 2009 Lundbeck announced the beginning of Phase I clinical trials for Lu 02-750 in a Press release. They anticipate regulatory filing probably after 2011.

Lundbeck is a global pharmaceutical company specializing in brain disorders. Although headquartered in Copenhagen, Denmark H Lundback A/S has employees worldwide through company acquisitions and development partners.

Lundbeck is also developing treatments for AD, Schizophrenia, Freidreich's Ataxia, Major depressive disorder. They also market medications for insomnia.

On an interesting note, Lundbeck is one of the few pharmaceutical companies listing non-medication treatments for Parkinson's disease.

The development of Lu 02-750 was apparently conducted under the direction of Professor Håkan Wikström who describes himself as a bio-professional geek. Professor Wilkstorm, is on the faculty of Groningen University in the Netherlands and is a co-founder Axon Biochemicals B.V.

About Lu 20-750 it has been reported that "In animal studies, (it is) the drug candidate shown to have a stronger effect on the disease than current drugs."
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News from Parkinsons Action Network about Health Care legislation affecting Parkinson's disease

First, on Saturday, December 19, the Senate gave final approval to the Department of Defense Appropriations bill, sending to President Obama a piece of legislation including $25 million for the innovative Neurotoxin Exposure Treatment Parkinson's Research (NETPR) program.

The NETPR program is the only Parkinson's-specific research program funded by the Federal government. Advocates must work to secure funding for this program every year, and the Parkinson's community rallied through a tough economy to ensure that the NETPR program did not receive a budget cut.

The second piece of legislation also took place on Saturday when the Cures Acceleration Network (CAN) Act of 2009, introduced by Senator Arlen Specter (D-PA), was included in the final Senate version of health care reform legislation. The CAN Act seeks to cut the time between discovery and development of new drugs and therapies. For some time PAN has focused on this troubling trend. Thanks to Sen. Specter's leadership and PAN advocates who contacted their Senators, a focus has been placed on accelerating tomorrow's therapies and drugs through the development pipeline.

The Senate expects to vote for final approval of the bill before Christmas, and PAN will work to sustain the CAN amendment during the Conference between the House and Senate.
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As of December 14, 2009 Azilect no longer carries the cheese effect warning.
You can read about in the Teva Pharmaceutical Industries Ltd press release
If you haven't read Dr Karl Kieburts comments about the ADAGIO study and the inconclusive results of the 2mg dosage as opposed to the positive results at 1mg, please take a look:

Link to the ADAGIO Study commentary by Karl Kieburtz, MD, MPH
There will probably be another differently drawn Azilect (rasagiline) study of the 2mg dose.
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June 2010 COGANE Update
Phytopharm PLC received a USA regulatory approval by the FDA to begin the Phase II Clinical Trial.
Patient enrollment should begin in late 2010
You can read the Phytopharm press release here
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Droxidopa from Chelsea Therapeutics International (Nasdaq: CHTP) Droxidopa is described as a pro-drug to treat neurogenic orthostatic hypotension (NOH)

"Droxidopa provided statistical significance in the treatment of Neurogenic Orthostatic Hypotension (NOH) improving the motility of these patients and reduced their risk of falls with a benign safety profile. These improvements were measured through an orthostatic hypotension questionnaire and corresponding clinical indications"

NOH is a drop in blood pressure resulting from deficient release of norepinephrine and is characterized by dizziness, weakness, blurred vision and fatigue.
NOH occurs in patients suffering from autonomic dysfunction and movement disorders such as Parkinson's disease, multiple system atrophy and pure autonomic failure.
Droxidopa is a synthetic catecholamine that is directly converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE in the nervous system, both centrally and peripherally.

In December 2009, a press release announced that a small subgroup analysis of 44 PD patients (all on L-dopa) and enrolled in Study 302, a Phase III withdrawal study, demonstrated a "more robust response compared to the overall population study."
"Study 302 evaluated the efficacy and safety of Droxidopa, a pro-drug that results in increased body stores of norepinephrine, in 101 patients with symptomatic NOH. All patients in Study 302 were evaluated for functional and symptomatic improvement through multiple endpoints including the orthostatic hypotension questionnaire (OHQ)."

Although Droxidopa is currently on the market in Japan, it is not on the general market in the US. In 2007 Droxidopa was awarded orphan drug status specifically to treat NOH in the US and in Europe. "for the treatment of symptomatic NOH in patients with primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine-ß-hydroxylase deficiency, or nondiabetic autonomic neuropathy"

Treatments for Parkinson's Disease

2009-12-11T22:43:00.015-05:00

Parkinson's disease is treated in several ways. And treatment is what is currently available; there are no sure-fire cures. Sadly, treatments often lose their effectiveness to combat the progression of the disease over the years.

To confound the problem of treatment is the fact that Parkinson's disease is a collection of syndromes with varied symptoms and progression rates. Treatment needs to be adjusted to the individual.

Knowledgeable physicians and proactive PD patients learn to be aware of when adjustments in dosage, timing, the addition of another medication to work with the current prescribed med can be effective in prolonging "on" times and reducing "off" times. And some are aware that nutritional supplements are as much a part of a therapeutic regimen as the prescription pad. Other physical therapies are acknowledged by advanced medical plans so that all you need is a prescription for a sessions which the patient can often continue.

So what are the options? Let's begin with a summary of prescribed medications by category. We'd love to post the handy-dandy medication chart we made listing product names, generic names, symptoms for use, contraindications, side effects and some general information about the way the medication works but, doggone it, we've been unable to transfer the table successfully to the blog-site. We're working on it. Today we're working from the printed version.

Prescription Medication:

DOPAMINERGICS are the most common - these have been the "gold standard" for many years but are not without problems and may not be the best choice for the newly diagnosed.

The standard treatment has been Sinemet (levodopa-carbidopa) This is still the first line treatment for the majority of patients but is losing some ground to Azilect

Levodopa is absorbed into the blood stream in the small intestine and converted into dopamine after in crosses the blood brain barrier. (note: dopamine cannot cross the blood brain barrier)

Problem: Levodopa has a short half-life and a major side effect is nausea which can last up to a year. A number of other problems can occur including hallucinations common to other PD meds.

The combination of levodopa-carbidopa improves the functioning of the levodopa, prolongs the "wearing off" meaning fewer side effects such as the dyskinesia-dystonia. It can also allow for a lower levodopa dosage.

Other dopaminergics include Madopar which is levodopa-benserazide hcl.
Carbidopa is also a dopaminergic - it inhibits the peripheral metabolism of levodopa prior to crossing the BBB.
For people who have trouble swallowing there is Parcopa (levodopa-carbidopa) which is orally dissolvable.

The most common immediate unpleasant side effect of dopaminergics is nausea which can last for up to a year but may be relieved by increasing the carbidopa. Timing is important and taking with a low-protein meal may reduce nausea. It is suggested that a regular protein meal follow Sinemet by at least one hour.

DOPAMINE AGONISTS - bind to different dopamine receptors - they are sometimes taken with antagonists because they have a short half life. The binding activates the dopamine receptor pathways.

I'm not going to list all but the most common include bromocriptine, Requip XL (ropinirole), Mirapex, Trivastal, and the Neupro Transdermal patch (rotigotine) returned to the European market last June but still off the US market although not entirely unavailable to US prescription holders)

DOPAMINE ANTAGONISTS are primarily used as anti-psychotics. They bind but they don't stimulate dopamine receptors - they copy the effect of DA.

COMT INHIBITORS - inhibit the catechol-menthyltransferase enzyme to inhibit the break-down of dopamine after its release in the brain. They begin to work immediately after the first dose. They are often combined with levodopa-carbidopa later in treatment. Common names include Comtan (entacapone) Tasmar (tolcapone and Stalevo (which is a combination of levodopa-carbidopa-entacapone)

MAOI-Bs are another category - Monoamine oxidase-B inhibitors or MAO-B inhibitors slow the breakdown of dopamine by inhibiting MAO-B enzyme. By this action, the dosage of levodopa-carbidopa may also be reduced.

Common MAOI-Bs include Selegiline or Eldepryl, Zelpar. These still carry the tyramine-cheese effect warning which is actually more common to MAO-As. There is also EMSAM which is a transdermal patch of Selegiline which is also approved by the FDA for treatment of Major Depressive Disorder. The 6 mg EMSAM patch does not carry a tyramine warning..

Another MAO-B which differs chemically from Selegiline is Azilect. Many people are turning to Azilect as a first line medication - before any other anti-parkinson's meds because it has shown to be very effective in slowing the progression of this disease. Currently there are trials to determine its effectiveness in being later combined with levodopa-carbidopa to reduce the "Off" times and to prolong the effective usage of levodopa/carbidopa. On December 14, 2009 FDA approved the removal of the tyramine warning from the Azilect label.

OTHER MEDS include off-label meds which have been effective for some people.

They include: Amantadine, an anti-viral which increases the release of dopamine.
DynaCirc CR - a calcium channel blocker or calcium agonist - which tries to restore the cells to a more youthful saline condition.

Note: it is thought that dopamine is forced into the cytoplasm prematurely and there it combines with misfolded alpha synuclein and calcium to create the gummy mess which causes the dopamine to die.
The Exelon patch - a reversible chlorinesterase inhibitor used for moderate dementia, cognitive skills loss and executive skills.

Aricept functions in a similar way but is still more common to Alzheimer's patients.

In the next category are the ANTICHLORINERGICS which block acetylcholine to compensate for that loss of homeostasis with the declining dopamine neurons. They are not as commonly used now but are the oldest of the modern PD meds.

A few names are Artane, Cogentin, Norflex, Benadryl.

I'm not going to list the ANTI-DEPRESSANTS and the various categories such as SSRIs but that is another category of PD meds and yes, we have another fussy table that won't transfer properly. But we will post it one day because it is helpful.

Okay, what's next? Many people would love to be able to use NUTRITIONAL SUPPLEMENTS or alternatives to conventional medication and there are a number of important supplements, but make no mistake, they too have side effects and can have an impact upon brain/body homeostasis - often the reason for use - unless contraindicated or mis-used.

Most of these nutritional supplements can be found in foods but to get the right amounts to fight free radicals we supplement. To get the optimal amounts of some nutritional supplements, we take capsules and tablets, powders and liquids. Often we could not possibly eat enough of a particular food and/or those food may also include other elements which in larger amounts might not be so beneficial. Remember also that for PwPs smaller capsules seem to work best unless you can find a chewable or better yet a sublingual that doesn't result in a burning sensation.

In this category are Antioxidants such as CoQ10. Another very important antioxidant for PD is glutathione in either sublingual, liquid or the expensive IV treatment. We'll be writing more on glutathione and N-Acetyl L-Cysteine. Vitamins C and E are antioxidants which work synergistically, even more so with the addition of Alpha Lipoic Acid. Vitamin A is well stored in the body but an occasional boost might not hurt either as beta carotene or as Vitamin A.

PwPs have deficiencies of certain B vitamins. A low dose of B complex (25-50 mgs max) might be in order. Otherwise B2, B5, B6 and B12 can be adjusted separately.

D3 will help to boost the immune system and for PD patients who don't get out into the sunlight much - there is no other alternative to producing Vitamin D in the body. Other supplements to consider are: Acetyl L-Carnitine which is sometimes found in combination with Alpha Lipoic Acid.

Creatine is not just for weightlifters and body builders, PwPs are taking it also.

You don't hear much discussion about mushroom extracts for PD immune system enhancers but Maitake, Reishi, Shitake and Astragalus can sometimes be found in a combination capsule (to keep the cost down).

For folks with digestive issues, consider ginger or Lactobaculis Acidophilus for a healthier GI tract balance. This is very important when diarrhea is an issue or after a course of antibiotics which also does a number on the friendly flora in the gut.

Omega 3 oil is another nutritional supplement. Another interesting source of essential fatty acids (EFAs) for PD is Coconut Oil. It has an unique combination of fatty acids and does come in capsule form if you don't find one with a decent taste for food preparation.

If you're not drinking green tea, there's a capsule for that and might actually be better for providing what you need without what you do't need. And if you don't cook with a good turmeric from India, it also comes in pills as well. The primary ingredient of turmeric is a powerful anti-inflammatory in the form of curcuminoids.

We don't have any experience with mucuna pruriens. You can obtain it as velvet or fava beans. It is also available in as seeds, powder, capsule or extract. The problem is finding the "dose" that works for you since much of it will be lost in the digestive process. Standardized doses may work more effectively and be safer. You can find it online as Dopabean from at least one company. Be wary of claims about the L-dopa content because many companies products are not standardized, making it very difficult to determine how much you need and to risk getting too much or too little.
9/2011 Addendum: Steve has some experience with mucuna pruriens now and we will be writing about it when he has used it for a longer period of time.

HEALTHY DIET for PD:includes items listed above as well as below.

You're going to have to make the adjustments to your medication schedule and the type and restrictions of those meds. For nutritional suggestions, some diets like the Mediterranean diet may be a bit healthier and use some very helpful seasonings. The focus here is on olive oil which actually enables utilization of nutrients from fruits and veggetables, fish rather than too much red meat, and red wine (in moderation).

don't forget the green and black tea or a few black walnuts a day.

MASSAGE THERAPY

Is invaluable on a regular basis. This is more than our opinion it has been clinically demonstrated. If you have the $$$$ and can afford it, 2 sessions a week would be ideal. One session would be good and less than that will see many reversals of the good done. Medical massage - Swedish Massage involves the entire body with focus on the problem areas and issues and really should be done by the same licensed therapist all of the time. Massage increases endorphin levels, works to break up muscle knots, reduces stiffness and alleviates pain caused by a variety of conditions. An important element in treating postural instability, massage should be on your therapy wish list. Unfortunately this valuable therapy is not recognized by most health insurers including Medicare. Other forms of useful massage include Shiatsu/acupressure, and Neutomuscular Therapy (NMT).

PHYSICAL THERAPY

Occupational therapy for assistance with tasks of daily living. Getting into bed, standing and sitting, buttoning a shirt, whatever. While this is not permanent on-going therapy, a patient will need refresher courses as the disease progresses. Care-givers should attend these sessions if permitted.

Exercise therapy can include a wide variety of therapies: swim, dance, yoga, tai chi, nautilus equipment, exercise bikes - especially motorized bikes for legs and arms, vocal exercises.

Forced Exercise: is a more recent concept but very exciting. If it you find access to the right equipment and can put in the required time, it might work for to reduce reliance on higher dosages of medication and to relieve some symptoms.

Voice therapy will include the very important breathing exercises to aid speaking, breathing, swallowing. If you can't get to a therapist, there are home exercises which will help.

OTHER TREATMENTS

As the disease progresses there is also Deep Brain Stimulation if the patient meets the qualifications and the physicians feel they are good candidates.

There are older surgical procedures but are not as commonly used in this century. More treatments and surgeries are in the pipeline. However, it was announced in October, 2010 that these older surgieries are still valid and moreover can be used with DBS with the understanding that there is a higher risk of depression with subthalmic nuclei surgeries.

While we are not convinced that any form of stem cell treatment performed now will have more than limited advantage, who wouldn't want to have that advantage for a few years? If successful, there appear to be reversals after a few years. The various forms of cell therapy are still works in progress and are still pipeline treatments.

Although not treatments, tools that can help the PD patient with activities of daily living are part of the therapy to assist unaided or semi-aided functioning. Special handled flatware, laser canes, shirts with snaps, cups that prevent spillage, walkers with baskets and seats, voice recognition programs and other computer programs to enable "typing", bath seats, higher toilet seats will be of use to many PwPs.

One last observation: a plan is needed that involves the dreaded "what if" stuff. How and who and when, where and why. Quite a bit of planning may be necessary for a disease which can render a person almost completely non-functional. Families need to discuss these matters with the patient in the beginning. Plans must be made to make the home safe for the PwP so that they can remain there as long as possible.

And plans must be made to relieve caregivers from time to time. I'd suggest weekly to be realistic to their needs. Several hours are necessary so that they can catch up with social activities, do shopping, spend some uninterrupted time with reading or email or just get a well deserved rest to make up for their own sleep deprivation.

Think what a wonderful Holiday Present some free time would be to someone who needs recharged batteries.

The Person in the Parkinson's Disease Mirror

2009-12-03T13:17:00.003-05:00

PD Setbacks and Moving Forward Again

Since being DXed with Parkinsons 6 years ago I've only had a mild progression of the disease. But about a year and 1/2 ago the progression set in more seriously. More stiffness and rigidity started setting in, more often swallowing difficulties, occasional symptoms on the "good" side of my body.

I'm no longer comfortable in my skin; I'm very uncomfortable in my facial expression. I've heard other patients describe their face as the Parkinson grimace. My wife says I don't have this, just not much expression. Yet, I can smile with my face and my eyes when I'm really happy or amused.

She's not happy with my voice again. The fact that the volume goes down near the end of a sentence is a longstanding problem - predates the PD and predates even our marriage - so we won't go there. The pitch of my voice is higher again. Which made me realize that I hadn't been doing my vocal exercises. I pulled out Mary Spremulli's Voice Aerobics DVD and did those Voice Aerobics right along with the class. My voice was better for the rest of the day. More volume, better inflection, deeper pitch. And I felt happier because I felt better about myself.

Self image is very important.
It isn't just what other's see.

How many of us dread looking in the mirror or seeing a reflection in a glass door because we don't know that person, we have a hard time being that person. It's bad enough going through the normal aging process.

Improving self image, helping Mother Nature while holding the line against Father Time involves exercise. Sometimes it feels as if my life revolves around exercise and in a way it does. So even though I go to exercize therapy 5-6 days a week, that's not enough. I've neglected the exercises I was doing at home between going to the therapy center. No more. Doing PD body maintenance can become full-time. And I admit that I do not want to have to maintain full time. I just want to be.... A luxury not granted to those with Parkinson's disease.

I realize now that when I stand up, I need to stretch before walking. I started doing head and neck stretches while seated at the computer. And I'm willing to ask my wife to correct me. Before she would just tell me, now I can ask. Healthier, I think, more positive.

It is so easy with Parkinson's disease to slip back into the "waiting to die" mode, to begin to feel that you have nothing to contribute. My wife reminded me this morning of the positive things I can do. Make your own list. Circumvent the PD depression. Find YOUR worthwhile inner person.

Addendum: Finding the positive is what you can do changes as the weeks and months go by. One one hand we need to be aggressive and on the other hand we need to accept what we are sure we cannot change.
It is so easy to become trapped within the dichotomy.

Neupro Availability Update for a Happy PD Thanksgiving

2009-11-26T14:38:00.009-05:00

A Neupro Patch and Parkinson's Disease Discovery

Wishing everyone a Happy USA Thanksgiving. We're trying to get ready for the family festivities but wanted to take a moment to share some information with you.

We found something for which people in the US who had been using the Rotigotine patch, also known as the Neupro Transdermal Patch, might be able to give thanks.

Because it is Thanksgiving day in the US, I won't be able to contact iBenefitRX to verify their statements of 6/30/09, but it appears that there is a way for those with a prescription might be able to order this medication without waiting for months and months for it to complete its second FDA process.

We are posting a link to their website article about being able to obtain Neupro through an affiliate. The rest of the work is up to you.

Here's the iBenefitRX link to Neupro and the direct link to Customer Service email.

We last wrote about Neupro in August 2009 when the prospects looked dismal but it turns out that we didn't ask the right questions. Thanks to Anonymous whose comments in the August article are worth a read, we've taken another look and that is how we found the information above. Let us know what happens.

And don't forget, if you like the turkey breast meat, play the PD card and explain that it is better for you...because it is. Let's hope the wishbone does its magic.

Happy Thanksgiving

2010 Addendum: There are other, longer established online pharmacies online. We found the site in the article quickly and set up a link but did not do more research. We have done some of it now but are not too happy with the results.

You might be interested in a few more and ways to verify the company you are considering.

Check company trail through a domain search This will tell you how long the site has been in use. You are looking for a legitimate existing business.

You can use the following links at the Canadian International Pharmacy Association (CIPA) to verify accreditation of the pharmacy you are considering.

to verify membership
or similar link to consumer safety

It is important to note that even fraudulent sites are sporting the CIBA seal and credentials, so do not take those at face value.

Note: TheCanadianPharmacy.com which is a legitimate site, does NOT carry the patch so the seal issue is very confusing.

Another site to check is The International British Colombia Pharmacy Association also has a list of requirements legitimate Canadian Internet Pharmacy must follow.
Also make sure that there is a legitimate street address as well as phone numbers. We did find 2 sites with exactly the same address. Of course many mailing stores offer mailboxes which come with a street and suite address. While prices were pretty similar at the two Toronto sites, one offered free shipping while the other did not.
One serious problem with ordering from a non-local store is that your credit card will be charged and you may never see the product. There are plenty of scam sites out there. At lease one purports to operate in Canada but are actually in Mexico. Others...who knows!