“Our results reflect the achievements of a team of bright scientists, at various stages of their careers, all intently focused on Parkinson’s. Their shared knowledge, creativity and collaboration advances our understanding of the disease. I am grateful to PDF for helping to make it possible.”
— Dr. Lloyd A. Greene, Columbia University Medical Center
PDF Grant Programs
Are you interested in furthering Parkinson's science? View PDF's open grant programs.
What can we learn by studying genetics and Parkinson's? PDF-funded researchers Drs. Mata and Zabetian share their progress six years after launching the first large-scale survey of PD genetics in Latin America.
Results: Center Grants Program
PDF supports three Research Centers with $2.36 million — more than 50 percent of our total research budget. Our support allows groups of scientists to collaborate in order to advance our understanding of Parkinson’s disease.
Browse highlights below:
PDF has supported the research efforts at Columbia University Medical Center since 1957. The center's researchers and doctors lead the field in science, training and impact in the study of Parkinson's. They have developed scales to assess the severity of Parkinson's, tested new drugs to treat the disease, and are leaders in uncovering the pathogenesis of the disease.
Recent grants have supported research in neuroinflammation, genetics, programmed cell death/GDNF in development of dopamine neurons, animal models utilizing toxins and gene alterations, molecular alterations of nerve terminal dopamine pools, neuropsychology, behavioral effects, epidemiology, clinical trials and evaluation of surgical procedures.
Highlight: Finding Potential Targets for Preventing or Treating Parkinson’s
Although the vast majority of cases of Parkinson’s disease have no known genetic cause, among those that do run in families, the most common mutations occur in the LRRK2 gene (leucine-rich repeat kinase-2). Now, researchers led by Ana Maria Cuervo, M.D., Ph.D., at Albert Einstein College of Medicine and David Sulzer, Ph.D., of PDF’s Research Center at Columbia University Medical Center, funded in part by PDF, have shown for the first time, why the faulty LRRK2 protein is harmful, and how it can block the normal cell recycling process. This research was published in the March 3, 2013, online edition of Nature Neuroscience and builds upon earlier work also funded by PDF.
Normal cells, including those in the brain, use a recycling and waste disposal system to stay healthy. The process — known as chaperone-mediated autophagy — begins when molecules called chaper- ones patrol for damaged proteins and then transport them to a recycling center (the lysosome). After arriving there, the damaged proteins travel to the interior region of the lysosome, where they are broken down into components that can be reused.
Drs. Cuervo and Sulzer showed that chaperone-mediated autophagy was capable of recycling healthy LRRK2 proteins, but it was not as successful in breaking down those LRRK2 proteins that had the mutation found in people with Parkinson’s disease. In addition, these faulty LRRK2 proteins then prevented other proteins, such as alpha-synuclein (a protein that causes PD), from getting broken down and recycled.
The studies of Drs. Cuervo and Sulzer over the years have spotlighted the need for developing therapies that can help restart or speed up cellular recycling — therapies that could potentially benefit people whose PD has no known genetic cause as well as those who have LRRK2 mutations.
Highlight: Scientists Discover Most Common Genetic Risk Factor for Parkinson’s
Lorraine N. Clark, Ph.D., and Karen Marder, M.D., M.P.H., two scientists supported at PDF’s Research Center at Columbia University Medical Center, have collaborated with a team led by Ellen Sidransky, M.D., of the National Human Genome Research Institute, to create one of the largest clinical investigations of the genetics of Parkinson’s ever undertaken.
Results of the study, published in the New England Journal of Medicine, demonstrated that people who carry a mutation in a gene known as GBA have a significantly increased risk — over five-fold — for developing Parkinson’s. (Mutations in the GBA gene have also been shown to cause Gaucher’s disease.) This makes the newly identified genetic risk factor for Parkinson’s the most common among the dozen or so genetic factors that have been identified to date. Mutations in the GBA gene most likely increase susceptibility to PD, which when combined with other factors, results in disease. The mechanisms by which this happens are not yet understood and require further research.
Another New York institution with an important program in Parkinson's research is Weill Medical Center, headed by Dr. M. Flint Beal. Since 2003, PDF has committed a third Center grant to support the research efforts of this group.
Highlight: New Tool Will Improve Testing of New Treatments
In PDF-funded labs at Weill Cornell Medical Center and Columbia University Medical Center, M. Flint Beal, M.D., and Robert Burke, M.D., have made progress in finding a new and powerful tool for testing new Parkinson’s therapies and studying the underlying causes of the disease.
Working with Chenjian Li, Ph.D., at Weill Medical College and Tinmarla Francis Oo at Columbia University, Drs. Beal and Burke have created a unique “mouse model” that ex presses a mutated form of the LRRK2 gene — the gene most commonly implicated as a cause of Parkinson’s. Their results were published in Nature Neuroscience. Their model will help scientists to create and test new Parkinson’s treatments in the lab. Prior to this development, progress in Parkinson’s had been hampered because scientists did not have a model that accurately mimicked the natural course of PD in humans.
Since 1999, PDF has supported the Rush Parkinson's Disease and Movement Disorder program in Chicago, IL. Basic and clinical research scientists at Rush work closely together in planning and executing projects dealing with Parkinson's. The clinical program is directed by Dr. Christopher Goetz, and the basic science program by Dr. Jeffrey H. Kordower.
Highlight: Using MRI to Better Understand Cognitive Impairment
Cognitive impairment is a common and troublesome nonmotor complication in Parkinson’s that can range from mild dysfunction to advanced dementia. The impact of cognitive impairment is felt both by people living with Parkinson’s and their care partners. Jennifer Goldman, M.D., M.S., of Rush University Medical Center has developed a research program that uses Magnetic Resonance Imaging (MRI) to examine whether there are changes in the structure of the brain that may accompany mild cognitive impairment and dementia in Parkinson’s. With PDF’s support, she conducted a pilot study of 30 people with Parkinson’s. Among those individuals who had the greatest cognitive impairment, she found a shrinkage in the brain regions that are implicated in memory function. By helping to identify those individuals who are most at risk for developing dementia, Dr. Goldman's research may provide leads to developing new therapeutic interventions for these people.