Overcoming Obstacles in Treating Parkinson's

June 1, 2011

One step at a time: Under Hood's leadership, the Michael J. Fox Foundation has worked to change how medical research works.

Dr. Mark Stacy Butch Usery

Why do some Parkinson’s patients in clinical trials respond favorably to drug treatments, even when they are receiving placebo medicines? Why do routinely prescribed Parkinson’s drugs cause a percentage of patients to start gambling compulsively, overeating, or engaging in high-risk behaviors? Mark Stacy, associate dean for clinical research at Duke’s School of Medicine and a Michael J. Fox Foundation (MJFF) grant recipient, is studying these and other questions vexing Parkinson’s researchers as they search for better treatments and, eventually, a cure.

Parkinson’s is a neurodegenerative disorder that causes dopamine levels in the brain to decline over time. The most frequently prescribed medicines for treating Parkinson’s are dopamine-replacement or -enhancing drugs; there is also a class of drugs called monoamine oxidase–type B inhibiters that give dopamine-replacement therapies the ability to be effective over longer periods of time. But because dopamine plays an essential role in a wide range of human behaviors and actions, both positive and negative (including memory, gratification, impulse control, and drug and alcohol addictions), dopamine therapies affect people in a variety of ways.

“In some Parkinson’s patients, dopamine therapeutics produce impulse control disorders, such as pathological gambling. It’s an abnormal reset of the reward response in the brain,” says Stacy. Determining why (and how) some patients experience the effect and others don’t has implications for understanding the complex connection between the physiology of specific patients and the development of safe and effective treatments.

Through an MJFF grant, Stacy is also overseeing a clinical study to assess the role that patient attitudes and expectations play in outcomes for treating dyskinesia, another common side effect of longterm dopamine replacement therapy that results in uncontrollable, involuntary writhing movements as the drugs become less effective over time.

Stacy says that research at Duke and elsewhere has shown that patients who are very religious or very optimistic may respond better to treatment than patients who aren’t. The attitude a physician has about a patient’s outlook can also have an effect—such as when a doctor oversells the efficacy of a treatment. In both instances, a patient may report that a drug (or placebo) is working and that symptoms are diminished, when they actually are not. The MJFF grant will focus on ways to minimize this bias in order to gain more precise and accurate information about how effective various Parkinson’s treatments are.