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Isn't Parkinson's Degenerative? How Can Michael J. Fox Be Better?

Actor Michael J. Fox in a 1988 photo (Wikimedia Commons)
Actor Michael J. Fox in a 1988 photo (Wikimedia Commons)

“Great news,” I thought when I read that Michael J. Fox was returning to a comic television role, 12 years after he left to focus on treating his own Parkinson’s disease and funding research to help all patients.

“But how can this be? If there’s a big breakthrough in Parkinson’s disease treatment, wouldn’t we have heard about it? And if there isn’t one, isn’t the definition of a degenerative disease that it goes downhill? How can he have climbed back up again?”

Dr. Michael Schwarzschild, a Parkinson’s expert and director of the Molecular Neurobiology Laboratory at the MassGeneral Institute for Neurodegenerative Disease, kindly fielded my questions. First the disclaimers: He is not involved in Fox’s treatment, and has received grant support from the Michael J. Fox Foundation for Parkinson’s Research. Now the answer to my first query: What could it mean that Fox told ABC he “kind of stumbled onto a new cocktail of meds” that made him better enough to work again? Dr. Schwarzschild:

I heard his quote, too, and of course it’s wonderful that he’s making a comeback. In terms of what to make of this somewhat cryptic comment, I don’t think it relates to some new treatment that others don’t know about, or something newly approved and dramatic, because there isn’t anything like that.

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'Someone can improve without breaking the laws of physics about Parkinson’s disease being an inexorably progressive disorder.'[/module]

As a clinician who treats patients with Parkinson’s, your impression is right: It’s a progressive neurodegenerative disease. On average, in typical or even not-typical Parkinson’s disease, it’s inexorable.

That being said, it’s not a constant decline even though it goes in that direction, and medication can have a huge effect. Levodopa, when it came around in the sixties and seventies, took people out of nursing homes. Usually, with someone who’s getting reasonable care, you don’t expect, late in the disease, to discover some combination of currently available medications that make a huge difference. But sometimes you do.

I’ll give you a couple of examples even with approved medications in the United States.

People will often get a good response to the standard medication and as the disease progresses they’re still getting a good response but having more and more symptoms. A substantial number of people develop a complication of medications called dyskinesias – abnormal involuntary twisting or flitting movements, which were on full display in some prior public appearances of Michael J. Fox.

For people who have that sort of problem, there are some medication approaches that can bring a dramatic benefit. There’s a medication called amantadine which is probably the only standard anti-Parkinson’s medication that can improve dyskinesias rather than make them worse. For most people with Parkinson’s, amantadine is not a first-line therapy because they don’t tolerate it that well or only in low doses, but for some it’s just the right combination where they tolerate it very well and it has a good effect on both their dyskinesias and their typical symptoms of Parkinson’s disease.

Surgery for deep brain stimulation is another example, where someone may be doing very poorly and for a subset of patients, the response is very good. Someone can improve without breaking the laws of physics about Parkinson’s disease being an inexorably progressive disorder.

Another example: Sometimes someone is on a standard drug regimen, and there’s a whole assortment of adjustments to that standard regimen: they can take a medication every few hours to smooth out their responses, or they can take a medication that will make the standard medication last longer. There are currently something like 12 medications that are approved for just the motor symptoms of Parkinson’s disease, and sometimes there’s a combination that will be very helpful.

So again, being completely naive to what the basis is for his improvement, it’s not crazy given the fact that our symptomatic medications, while only partially helpful, can be helpful and sometimes dramatically so, either alone or in combination.

[module align="left" width="half" type="pull-quote"]It can be worth it to pursue trial and error — carefully.[/module]

It’s also probably a good example that when things get complicated and advanced, it’s good to work with a clinician who has some experience with that arsenal. It can be worth it to pursue trial and error — carefully.

So is that potentially the broader lesson, I asked, to to keep trying?

It could be that this reinforces the idea that you shouldn’t give up. Even the medications we do have — although they’re not good enough and we need to strive to improve them — we still have the benefit in Parkinson’s disease of some very effective medications. And for the right people in the right combination, it really can make a difference, to work with your physician to find that right mix and balance.

And the pipeline for possible new medications?

There’s a tremendous amount of hope, and the pipeline is not bad. But there’s nothing on the verge of FDA approval despite exciting earlier stage prospects. There’s a range of novel candidate therapies under investigation, from gene therapy to antioxidants to modifications of old things in new forms that can impact the dopamine system, like caffeine.

One thing I’ll mention: An example of something that is close and a surprisingly good example of using what we have available more effectively to make a big difference: There’s a new formulation for levodopa given continuously by pump. It’s on the market in Europe and undergoing FDA review here. The preliminary reports from higher-level clinical trials look quite remarkable. These are the kinds of things that, even later in the disease, for patients who have fluctuations, can make a big difference.

This program aired on August 23, 2012. The audio for this program is not available.

Carey Goldberg Twitter Editor, CommonHealth
Carey Goldberg is the editor of WBUR's CommonHealth blog.

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