Parkinson's Disease News Updates: August 2010

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.

Addendum April 2012: The FDA finally approved the Neupro patch and UCB anticipates a return to the US market in July, 2012

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.

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

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.

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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.

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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"