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Spotlight on Research Supported by PDF

Profile of Lorraine N. Clark, Ph.D.
Assistant Professor of Clinical Pathology
Dept. of Pathology and the Taub Institute
Columbia University, New York, NY

One of the great mysteries in Parkinson’s revolves around why people develop the disease. In recent years, genetic studies have offered important clues to answering this question by identifying several genes that are important in Parkinson’s disease (PD) and mutations that are more prevalent in certain populations. PDF supports important research in this area through the work of Dr. Lorraine Clark at Columbia University Medical Center and the Taub Institute.

Dr. Clark began her collaborations with PDF in 2003 when she was awarded a career development grant to study the frequency and distribution of mutations in Parkin — a gene that has been implicated in PD — among early-onset Parkinson’s patients. Mutations in Parkin are estimated to account for as much as 50 percent of cases of familial Parkinson’s (meaning there is a family history of PD) and 18 percent of cases of sporadic PD (with no reported family history). This study, published in 2006 in Archives of Neurology, was the first to compare a control group with the patient group and uncover that having a single (heterozygous) mutation in the parkin gene increased risk or susceptibility for Parkinson’s.

In her recent endeavors, Dr. Clark has examined what genetic mutations place certain populations at risk for developing Parkinson’s disease. In an ongoing study funded by the National Institutes of Health (NIH), entitled Glucocerebrosidase Mutations and Parkinson’s Disease in the Ashkenazim, Dr. Clark and her colleagues have identified specific mutations in the GBA (ß-glucocerebrosidase) gene that are associated with Parkinson’s disease in the Ashkenazi Jewish population. Currently in press for Neurology, Dr. Clark and her colleagues’ work suggests that the GBA gene may be a susceptibility gene for PD in other populations worldwide and is not just found in patients of Jewish ancestry. This study also shows that glucocerebrosidase mutations may increase the risk of Parkinson’s, that mutations may modify the age of onset to be earlier in life and may also be a risk factor for dementia or cognitive decline associated with parkinsonism.

Dr. Clark is currently collaborating with Dr. Karen Marder, of Columbia University, in a genetic epidemiology study of Parkinson’s disease and the role of parkin mutations (CORE PD). They are also conducting a large-scale genetic initiative to identify PD genes. Funding is provided by PDF and NIH.

Dr. Clark’s work is supported as part of PDF’s Center Grant to Columbia University of $2.6 million for fiscal year 2008.