This article originally appeared in the Spring 2010 edition of PDF's quarterly newsletter, News & Review.
“Why do some people who carry genetic mutations associated with Parkinson’s disease (PD) never develop PD while others do? What can everyone else do to join this group … thereby to prevent or reverse PD?” asks Roy N. Alcalay, M.D.
A postdoctoral fellow at the Center for Parkinson’s Disease and Other Movement Disorders directed by Stanley Fahn, M.D., Dr. Alcalay, along with his mentor Karen Marder, M.D., M.P.H., is trying to find the answer to this question as part of their work studying “phenotypes” of Parkinson’s. For Dr. Alcalay, this research follows a fellowship in movement disorders, which he also performed at Columbia under the PDF grant.
His and Dr. Marder’s research flows in part from the observation, widely accepted among people with PD and doctors alike, that Parkinson’s symptoms and prognoses can be very different from one person to the next. Scientists theorize that there may be several subtypes of PD and that this variability could account for these visible differences among the people who live with it.
To better understand this theory, Drs. Alcalay and Marder have worked with colleague and molecular biologist, Lorraine Clark, Ph.D., to study people with and without Parkinson’s. As part of a project called Consortium on Risk for Early-Onset Parkinson’s Disease (CORE-PD), they were able to track nearly 1,000 individuals, including three groups with genetic mutations that can lead to PD: Ashkenazi Jews (those with an Eastern European background); people with very early-onset Parkinson’s (under age 30); and people who have a first-degree relative with PD.
The researchers have found evidence that profiles of PD do exist, at least in these groups with genetic mutations. For instance, they have observed that people carrying a mutation in a gene called GBA tend to report cognitive issues earlier on in their Parkinson’s than do people in the other two groups, while individuals carrying a certain mutation in the LRRK2 gene demonstrate more trouble with gait and postural difficulties. (To learn more about this research, browse the News in Brief section of the Spring 2010 newsletter).
How do these profiles help us? While they represent the very beginning of this research, Dr. Alcalay hopes that over time they may lead to the development of new treatments and better use of current ones. For instance, if you and your doctor knew just what your future with PD could be like, it might be easier to assess which are the treatments that would work best for you.
But the most exciting prospects are the clues that researchers might find by looking at people who carry certain mutations, but then never develop PD. Do they have a protective factor? How can everyone else protect themselves? Should they make certain lifestyle changes, or are there specific medications which may prevent or delay Parkinson’s?
As Dr. Alcalay says, “These answers are still far off. But with this fellowship that PDF is so generously sponsoring, we have been able to pursue the theory that maybe Parkinson’s disease is made up of several subtypes that need to be treated differently. This could be an exciting pathway to follow.”
Dr. Alcalay’s fellowship at Columbia University is supported by PDF’s Center Grant to the University. In 2010, this grant will total over $2.7 million.