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New Methods to Predict, Prevent and Halt Parkinson’s Disease

Dr. Jim Maraganore April 28, 2010 12:00 PM This chat has ended. Thank you for participating.
Moderator (Moderator) - 11:59 AM:
Welcome! Today’s chat: New Methods to Predict, Prevent and Halt Parkinson’s Disease. Please start submitting your questions and Dr. Jim Maraganore will begin answering them as soon as we get started. While you are waiting for the chat to begin, feel free to visit our Neurosciences Pages to obtain more information.

Dr. Jim Maraganore (NorthShore) - 12:05 PM:
Hello! This is Demetrius M. Maraganore, MD. I am the Ruth Cain Ruggles Chairman of the Department of Neurology at NorthShore University HealthSystem. Prior to coming to NorthShore, I had spent 24 years at the Mayo Clinic in Rochester, MN. There, I was a Professor of Neurology and Chair of the Division of Movement Disorders. I was the Principal Investigator of a large research team dedicated to discovering the genetic and environmental causes of Parkinson's disease. We were fortunate to receive more than $20 million of funding from the National Institutes of Health, the Michael J. Fox Foundation, and other sources over 15 years. This work led to the discovery of methods to predict and treat Parkinson's disease. I also lead a global consortium of investigators, committed to studying the genetic causes of Parkinson's disease. The consortium includes 40 sites from 23 countries and 6 continents. More than 50,000 subjects are enrolled in our studies! Let's chat!

Tomas (Chicago, Illinois) - 12:06 PM:
How fast does Parkinson’s progress?

Dr. Jim Maraganore (NorthShore):
I am fascinated by this question! Typically, Parkinson's disease (PD) progresses very slowly over several years. However, the rate of severity can be variable, as well as the long term outcomes. For example, some PD cases can survive free of dementia or nursing home placement, while others not. We have no established method of predicting the outcomes of our patients with PD, or their rates of decline. We have no established methods of slowing the rate of progression or preventing unwanted outcomes. I have dedicated the next 20 years of my career, to be spent at NorthShore as the Chair of Neurology, to addressing these unmet needs. For example, to the extent that our DNA is our destiny, we aim to discover DNA fingerprints from blood samples that will predict outcomes and the rates of progression or the responses to therapy for our patients. We can then target new therapies against these genetic (or molecular) factors, with hopes of cheating destiny.

John (Glenview) - 12:11 PM:
What drugs do you find get prescribed (possibly by multiple doctors) that interact negatively?

Dr. Jim Maraganore (NorthShore):
The most effective treatment for the symptoms of Parkinson's disease (PD) is carbidopa/levodopa ("Sinemet"). Generally, it does not interact with other drugs adversely. The drug that poses the greatest concern is one called rasagiline (Azilect). It inhibits an enzyme in the body called MAOb. However, sometimes it also inhibits similar enzymes in a non-selective fashion. There is a long list of drugs and even of foods that should be avoided when using this drug. The risk is that the interactions could cause dangerous increases in blood pressure, potentially contributing to stroke or heart attacks in extreme cases, or rarely even death. Probably, the risks of this drug and its interactions are exaggerated. Nevertheless, in light of such risks (even if theoretical), the high costs, and the limited effectiveness of the drug, I am inclined not to use it in my practice.

John (Glenview) - 12:17 PM:
Will a stem cell (or other cure) be available in the next 5-10 years?

Dr. Jim Maraganore (NorthShore):
I think that in the next 5-10 years, we will have effective methods to slow or halt the progression of Parkinson's disease (PD). These are drugs that will reduce the production of a protein in the brain called alpha-synuclein (SNCA). Many such drugs are under development. However, I do not expect that stem cells will be a curative treatment. First, we do not understand the underlying biology of cells. What factors tell cells how much to proliferate and when to stop; where to migrate; and with which other cells to connect? Furthermore, the cells in the brain that succumb to PD are located in many different regions. It is not a simple matter of "replacing a part", but rather replacing multiple parts diffusely in the brain. We do not have effective or safe methods of distributing stem cells to multiple locations.

Nancy (Evanston, IL) - 12:21 PM:
How does one participate in a clinical trial? Is it through the office of my neurologist?

Dr. Jim Maraganore (NorthShore):
Typically, clinical trials for Parkinson's disease (PD) cases are led by neurologists. Most neurologists do not participate in clinical trials. Therefore, it is important to seek the care of a neurologist who specializes in PD. We call such doctors "movement disorders specialists". At NorthShore, we have several active clinical trials for PD, both medical and surgical.

Dr. Jim Maraganore (NorthShore) - 12:27 PM:
A vision for neurology at NorthShore... In ancient times, the leaders of Greece would visit an oracle, to receive prophecies of the future. What can I expect to happen? What can I do to alter the path of my destiny? The oldest oracle of Greece was at Dodona. Priestesses would interpret the rustling of the wind through a sacred oak tree. Based upon these subtle variations in the oak leaves, they would predict the future and advise correct actions to be taken. Just as at D-odo-N-A, we can interpret the subtle variations in DNA, the tree of life, to predict the medical outcomes of our patients and the correct actions to be taken. This is my vision for research in our Department at NorthShore. Specifically, we will discover the art of medical prophecy and provide our patients with molecular prognostics and therapeutics for several neurological diseases (Parkinson's disease and beyond).

Jen (Northbrook) - 12:28 PM:
Is Parkinson's Disease hereditary?

Dr. Jim Maraganore (NorthShore):
Great questions! I have spent the last 24 years of my life dedicated to the answer!!! Rarely, several members in a family develop Parkinson's disease (PD). In these families, we have been able on occasion to identify typographical errors in the genetic code (DNA mutations) that are the cause of the disease. However, these mutations are typically very rare in the general population. By contrast, we have been able to identify common genetic variations (polymorphisms) that slightly increase or reduce the risk for PD in populations worldwide. The most important of these genes encodes a protein called alpha-synuclein (SNCA). We have used this information to develop a treatment that reduces SNCA production and that holds great promise to halt or slow the progression of PD for all patients. Generally, if you have a first degree relative with PD (parent or sibling or child), your risk is doubled. However, that still constitutes only a 4% lifetime risk for PD.

Tomas (Chicago, Illinois) - 12:32 PM:
What factors may contribute to the risk of developing Parkinson’s?

Dr. Jim Maraganore (NorthShore):
There are environmental factors that are definitely associated with Parkinson's disease (PD). For example, persons who are exposed to pesticides or who have had a concussion or other head injury are at increased risk. Curiously, persons who smoke are at a reduced risk for PD. However, smoking is harmful. We believe that a metabolite of nicotine, called cotinine, may mediate the protective effect. We recently presented that work at the American Academy of Neurology. Maybe we can administer cotinine directly to patients, and bypass the harmful effects of cigarettes. There are also genetic factors that are associated with the risk of PD. We were the first to show that common variations in a gene called alpha-synuclein, or SNCA, are associated with the risk for PD in populations worldwide. This observation has been replicated time and time again. We have used this information to develop a treatment for PD that reduces the production of SNCA.

John (Glenview) - 12:37 PM:
For those PD patients you have been working with for for over 3 years, what Medicinal approach seems to lessen the symptoms (tremor, dyskinesia, etc.) the best?

Dr. Jim Maraganore (NorthShore):
If I were being sent to another planet to treat PD patients, the only drug I would take with me in my space ship, if limited by space, would be carbidopa/levodopa ("Sinemet"). It far outperforms all other drugs in treating the symptoms of PD. There is even data to suggest that it might slow the progression of PD (albeit modestly). Lots of doctors are afraid to use Sinemet, because they do not understand its benefits or how to manage or prevent its side effects. Patients who come to see me are often first treated by other drugs that are much more expensive, much less effective, and associated with more serious side effects (e.g., compulsive gambling or shopping or sexual behaviors). Other patients come to see me on too low of a dosage of Sinemet, or on doses that are taken too infrequently. By simply starting patients on Sinemet or dosing them properly, I am often the maker of miracles for my patients. I find that very gratifying!!!

Marie (Evanston) - 12:42 PM:
Are there any alternative therapies you recommend to compliment traditional treatments?

Dr. Jim Maraganore (NorthShore):
This is a very interesting question! There are some foods that naturally contain high doses of levodopa. Levodopa deficiency in the brain is what causes PD symptoms (slowness, stiffness, tremors, unsteadiness). One such food is fava beans. Good luck finding it in US supermarkets! :) Even if you find it, beware. Some people develop severe anemic reactions to fava (especially persons of Mediterranean decent). Fortunately, this is rare. Further, it is hard to titrate the dose of levodopa that is present in foods. Pills are of standard dose. Another interesting dietary substance is inosine. It increases urate in the blood. Raised urate has been associated with a reduced risk for PD. However, raised urate may increase risk of dementia or heart disease! Vigorous exercise may also benefit PD patients. This is because exercise increases the production of growth hormones in the brain. More research is needed to understand the mechanisms by which exercise benefits PD patient

Tomas (Chicago, Illinois) - 12:48 PM:
What are the side effects of Levadope?

Dr. Jim Maraganore (NorthShore):
The short term side effects are nausea, lightheadness, involuntary movements ("dyskinesias"), or hallucinations. They are all fully reversible with simple dose reductions. The long term side effects are a by product of disease progression. They include dyskinesias and also early wearing off of doses ("dose failures"). In most patients, these side effects can be managed through adjustments of the levodopa dose, or by adding a second or third drug to smoothen the response or to reduce side effects. In extreme cases, deep brain stimulation surgery can reduce side effects (dyskinesias, wearing off), allowing patients to use levodopa more effectively.

John (Glenview) - 12:52 PM:
How important is exersize in slowing the deteriorating process of PD?

Dr. Jim Maraganore (NorthShore):
I recommend that all patients do an aerobic exercise for 30 minutes or longer every other day (~ 4 times a week). The goal is to keep the heart rate above 100 for 30 consecutive minutes. In addition to benefiting energy and long term survival, exercise increases growth factor production in the brain. Growth factors may protect brain cells from degenerating, and hence slow the progression of PD. I also recommend that all patients do some type of stretching and balance exercise program twice daily, for 10 minutes. This would include yoga or Tai Chi. This helps to keep the limbs limber, the posture erect, and the balance sound.

Moderator (Moderator) - 12:52 PM:
Thank you everyone for your great participation, the chat will be ending in approximately five minutes. Please submit any final questions you have.

John (Glenview) - 12:55 PM:
Do you have an opinion on the use of CoQ10?

Dr. Jim Maraganore (NorthShore):
The court of medical evidence is still out. Maybe it slows disease progression, albeit modestly. There are ongoing studies.

Dr. Jim Maraganore (NorthShore) - 1:03 PM:
Thank you all for your questions! I am passionate about the treatment of patients with Parkinson's disease (PD) and I have committed my life to developing methods to predict, prevent, and halt PD and other neurological disorders. We are making great progress. We have identified risk factors for PD. We are developing new drugs to slow or halt its progression. But more work is needed! I am proud to work for NorthShore, where we have an outstanding Movement Disorders program. There are several active clinical trials. We are leading the world in identifying the genetic causes of PD, and in developing a Nobel prize winning technology called RNA interference as a method to slow or halt the progression of PD. We are also taking advantage or our award winning and nation leading electronic medical record system, to conduct innovative clinical research studies that will identify predictors of disease outcomes and new disease modifying therapies.

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