Slowing the Progression of Parkinson's

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A recent study from Northwestern University has identified a possible new drug for people with Parkinson’s disease. Isradipine, a drug used to treat high blood pressure, has the potential to slow the aging of dopamine cells, whose death in the brain leads to the devastating disease.

Dopamine is a vital chemical messenger in the brain that affects the control of movement. When large numbers of dopamine-releasing neurons die, movement becomes difficult.

Medill Reports spoke with the study's lead researcher, D. James Surmeier, Nathan Smith Davis Professor and chair of physiology at Northwestern University's Feinberg School of Medicine, about the study's findings and implications, and other research in the pipeline.

D. James Surmeier (photo by Tavaner Bushman/MEDILL)D. James Surmeier (photo by Tavaner Bushman/MEDILL)How did you get into physiology and neuroscience?
I was in a mathematics program at the University of Oregon and I got interested in modeling how the brain works. I decided to take a leave from my PhD program in mathematics to do some experiments and constrain some of the models that existed in the literature. I didn’t ever go back because it turned out to be so interesting.

I think a lot of us wonder why we think the things we do, why we act the way we act. I thought by studying neurons and the brain I might be able to learn something about that. It’s just an exciting thing to do with my life.

It is an exciting field, and a hot topic.
I think people are fascinated by the brain, and there is also a lot of interest in diseases of the brain, particularly aging-related diseases. I’m part of the baby-boom generation – we’re all getting to our late 50s and 60s and thinking about how age and time are affecting our brains.

There have been fundamental discoveries in the last 20 years that have really changed the way we think the brain shapes our behavior. The more we know, the more excited we are about it, and the more possibilities we see.

What is the most important thing you are coming away with from your study recently published in Nature?
The most important thing for the general public is that it points – I think – very clearly to a potential neuroprotective treatment for Parkinson’s.

Parkinson’s disease is the second most common neurodegenerative disease in the U.S. There are more than one-million people who are diagnosed with Parkinson’s disease, and that number is expected to grow to two-million in the next 15 or 20 years because of the aging population.

The symptomatic therapies for Parkinson’s disease given soon after diagnosis are really pretty effective. But because these therapies rely upon the remaining dopamine cells and don’t slow the progression of the disease itself, they are effective for only a relatively short period of time. If we had a strategy to slow the progression of the disease, we could significantly widen the duration of time that current therapies are helpful.

We are hopeful that isradipine or a drug like it will protect dopaminergic neurons and slow the disease. Isradipine is attractive in part because it has been used safely for decades to treat hypertension. The other important point of our study is that we link the actions of isradipine to mitochondria – the powerplants inside neurons. There is a large body of evidence implicating mitochondria in Parkinson’s disease. What wasn’t known was why mitochondria in dopaminergic neurons should be particularly vulnerable. Our study provides an answer. The other point worth mentioning is that we think isradipine can protect dopaminergic neurons without compromising their ability to do their job.

From the current phase-two clinical trial, how long until isradipine would be a legitimate therapeutic treatment?
Once the phase-two trial is complete in mid-2011, we will ask the National Institutes of Health to support a phase-three efficacy trial. We are already in discussions with them about it, and they are very interested because there is nothing that is known to slow the progression of the disease. They recognize that it is a major health problem.

Is there any hope for people currently living with Parkinson’s?
In principle, this therapy is designed for people in the early to mid-stages of the disease. If the symptomatic therapies are working at all, then the answer is yes, because that means there are still dopaminergic neurons around.

For latter-stage patients, there are other promising lines of research. Deep brain stimulation is an option. We are also part of a consortium of groups working on the development of induced pluripotent stem cells – stem cells taken from a mouth swab – that could be induced to become dopaminergic neurons suitable for transplantation back into the brain. This is a very promising area of study but it is a little further down the road.

Do you have a personal interest in Parkinson’s?
I had an uncle that died of Parkinson’s disease. This has pushed me. I remember him very well, and I remember his struggles and the impact his disease had on my family. There are nights where I’d just as soon go to bed that I stay up and work in part because I remember him.

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