Showing posts with label Deep Brain Stimulation. Show all posts
Showing posts with label Deep Brain Stimulation. Show all posts

Thursday, March 26, 2009

Parkinson's Blue Light District

Optogenics and the G-protein coupled receptor - what will it mean for PD?

It all begins in the brain, that complicated computer which processes analyzes, sorts, stores, and relays electrical impulses to keep the body functioning as designed. Sometimes, however, things go wrong, small parts malfunction, current varies to affect operation and the body human begins to get error messages. On many occasions we reboot, clean up some programs, add a program and we're good to go. Or we call IT or MIS and those specialists can fix many problems. But at other times the error messages persist.

Parkinson's disease sends some of those errors messages. The specialists here have been able to take patients to the edge of state of the art with medications which abate progression, which go to the source to make some symptoms ease or stop for awhile, but the disease remains. New treatments were developed to control the symptoms by interrupting the error messages. From radical surgery to invasive but less radical surgery, some patients have found relief while others were the same or worse.

We already know that not all PD patients are eligible for Deep Brain Stimulation (DBS) and that it appears to be effective for some but not all of the people who do receive the treatment. Ongoing research in an area called optogenics may become a way to change some of that situation by employing a method which allows for more precision in the surgical procedure by prior identification of the neurons which would benefit from stimulation. Basically the focus become tighter and more accurate before the nodes are set. One goal is to improve the results of DBS.

While aspects of the area of science now called Optogenics have existed for several years, the older apects are now being combined with a method developed in Karl Deisseroth's lab. By inserting a small fiberoptic cable into the brain the light impulses can be controlled as they search for the affected neurons. This procedure allows for smaller and smaller targets of the G-protein on the specific neuron.

The current procedures were developed by under the direction of Karl Deisseroth, MD, PhD at Stanford University. The project required the work of bioengineering and medical neuroscience and neurology students and faculty as they explored target after target to finally find that stimulation of the axons that connect the subthalmic nucleus are actually in areas closer to the brain's surface. While treatments would be still invasive, they would be less invasive thanks to better targeting at the G protein coupled receptors at the cell surface.

At Stanford University scientists were able to incorporate the technique in model mouse brains to produce activity in a real-time frame using both blue light to signal activity and yellow light to stop. The cells returned to their normal status unchanged at completion.

An interesting thing about neurons is that they communicate in a manner similar to binary code. Sometimes on sometimes off similar to the 0s and 1s of binary code. By being able to communicate in their on-off patterns, learning the neuron language might enable direct actual neural instruction through the flashing of the blue and yellow lights. In another metaphor, Optogenics appears to be the cell tower, now what is needed is a phonebook.

Optogenics holds hope for spinal cord injuries, restoring function to paralyzed limbs, allowing for new therapies, closely targeted pharmaecuticals and possibly become a neuronal therapy in itself.

Optogenics: A process by which brain cells can be activated by specific light
Channel Rhodopsins (ChR): light-activated ion channels appear to be coupled with the photoreceptor so that they do not require chemical signalling but instead are triggered by light.
Channel Rhodopsin (ChR2): algae-derived gene protein which makes neurons more active upon blue light exposure. Currently vector-introduced to the desired neurons. This is the "emit a signal" protein
Halo-rhodopsin (NpHR): from a microbe which can make neurons less active. The instruction here is to "stop emitting." They respond to yellow light.
G protein coupled receptors (GPCRs): signalling proteins found on the surface of nearly all cells.

Reading List:
http://storybank.stanford.edu/stories/controlling-brain-with-optogenics
http://www.newscientist.com/article/dn16807
http://www.freepatentsonline.com/7488583.html
http://pubs.acs.org/cen/science/86/8612sci1.html
http://www2.hu-berlin.de/biologie/expbp/Homepage-new_10408.pdf
http://web.mit.edu/newsoffice/2007/brain-block.html
http://med.stanford.edu/news_releases/2009/march/deisseroth.html
http://storybank.stanford.edu/stories/neural-traffic-light-a-go-better-brain-research
http://www.medicalnewstoday.com/articles/143132.php
Targeting the Brain's GO pathway  - 2010

In 2014 a small clinical trial for use of CBD oil for seizure disorders was published. It is referenced because of the explanation of the G-protein.
You can now find numerous optogenics studies.
You might also enjoy this article about Karl Deisseroth
2015 Optogenics study: Illuminating Parkinson's Therapy with Optogenics
 

Wednesday, March 25, 2009

DBS Surgery Basics for Parkinson's Disease

Treatments for PD: Deep Brain Stimulation

We already know that not all PD patients are eligible for Deep Brain Stimulation and that it appears to be effective for some but not all of the people who do receive the treatment. DBS is used in some advanced stages of PD that do not respond well to meds in order to reduce tremors and involuntary movement. It is used in younger and older patients alike. According to CNN, more that 35,000 people have undergone the procedure worldwide. According to one study when successful, DBS a 71% showed an increase in "on" time to about 4.6 hours. In that study about 40% of the patients demonstrated some adverse affects.

Deep brain stimulation (DBS) is a surgical procedure which consists of implanting high frequency electrodes in the subthalmic nucleus (movement center) in order to stimulate neurons to produce brain-derived neurotrophic factor (BDNF) through an implanted pacemaker-like device. Essentially the surgery when successful interrupts the faulty signals of dopamine cell loss. It targets the subthalmic nucleus, thalmus or globus pallidus as predetermined through an MRI or CT. The result is that many Parkinson's patients who receive the treatment find that they require less medication for the PD symptoms they have. The PD treatment is given unilaterally to many patients, bilaterally to others. Some opt for one side only to determine who it will work for them.

The complicated procedure is not without its negative side effects in some cases. There have been neuro-cognitive changes even when there is improvement in motor function. Depression, falls, gait disturbance, motor dysfunction, dystonia, balance and cardiac issues are also side effects in some patients. Sometimes there are infections at the pacemaker site which is usually in the chest. These symptoms may depend upon where the electrodes are placed. If Optogenics is developed to the point of state of the art for PD and use in DBS, we will certainly see far more precision in the placement of the electrodes.

The procedure itself occurs under local anesthetic so that the patient can be awake. The patient's head is immobilized in a frame and an MRI is done to pinpoint where the electrode is to be implanted. Two incisions are made in the skull and the microelectrode is passed into the brain. Current is passed through the electrode and increased while the patients responds to questions and performs certain movement tasks. After trial and error, the correct location is determined and the permanent electrode is placed and secured. The hospital stay is usually a few days.

After the swelling has subsided usually about a week later, the neurostimulator wires are connected to the electrodes. The pacemaker is placed usually in the chest. It may be another two to four weeks before it is turned on. In theory the patients can control the current flow through the pacemaker which is usually implanted in the patient's chest. In actuality the patient meets with the neurologist several times for stimulator adjustment.

The stimulation can be adjusted or turned off unlike the thalamotomy which Michael J Fox underwent seven years after his diagnosis, DBS is reversible in that it can be turned off or adjusted as in cases where tremors recur. When sucessful, the results of DBS can be a radical and remarkable change.

DBS is being used as an alternative therapy to thalamotony and pallidotomy which are permanent irreversible surgical procedures, It is used for control of PD tremor and control of essential tremor. It is being investigated for primary dystonia (involuntary muscle contractions) as well as for intractable epilepsy, cluster headaches which are usually vascular and associated with high blood pressure, chronic intractable pain, morbid obesity and obsessive-compulsive behavior (OCD)

One thng that is important to remember if you are considering Deep Brain Surgery is the Neurosurgical Team that will be performing the surgery. Don't be afraid to ask those questions about their experience and track record. Patients need to be proactive about their treatments.

DBS is not an inexpensive surgery. Costs can vary from $50,000 to $120,000 although in many cases are covered by Medicare and private insurance. Nonetheless, the co-pay can be very high.

In most clinical trials, patients with atypical symptoms, surgical contraindications such as MRIs or past PD surgery are excluded. Most studies will take both genders up to 75 or 80 years of age. What is necessary is that patients must fully disclose their medical history which includes psychiatric history; a desire for the surgery without full disclosure can lead to unexpected side effects.

So who does DBS work for or rather why does it work? How are the cells calmed or stimulated by the electrical shocks they receive? That still isn't clear but researchers in Scotland are exploring the idea that by stimulating other areas perhaps they can affect postural symptoms and gait issues also. One thing that is known is that when successful, DBS can improve the quality of life for the recipient.

Addendum:
On April of 2009, 50 DBS experts assembled to share experiences with Deep Brain Surgery procedures. They reached a consensus, per a recent news release issued by the UCLA Los Angeles Newsroom on October 10, 2010.

The findings include the best candidates for DBS; the importance of having an experienced team with an expertise in stereotactic neurosurgery performing the surgery. For some patients, DBS can be used for patients who have had PD surgeries. It is important to remember that certain treatments of the subthalmic nuclei can increase depression. And a reminder that surgery has complications with infection ranking highest.

You can read the full news release at the UCLA website.

References:
The first link is for DBS clinical trials - both closed and recruiting.
VIDEOS about DBS
You can watch video clips for PPN, dystonia and tremor.
And have your choice of many clips at YouTube.
If you live in Norway, there is a DBS clinical trial currently recruiting:
Clinical trial BCT00855621
Contact: Dr Mathias Toft 4799514189
Open to: 18-75 years
Gender: both
To study motor function, quality of life and cognitive function
Who is a good candidate for Deep Brain Stimulation
The medical history of DBS

Coming next:
Spinal Cord Stimulation
Optogenics
Magnetic Stimulation