Can we predict who is at risk of facing cognitive issues in PD and address them earlier? These are the questions being pursued by Dr. Goldman of the PDF Research Center at Rush University Medical Center.
PDF Grant Programs
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Results: Center Grants Program
ďOur results reflect the achievements of a team of bright scientists, at various stages of their careers, all intently focused on Parkinsonís. Their shared knowledge, creativity and collaboration advances our understanding of the disease. I am grateful to PDF for helping to make this possible.Ē ó Dr. Lloyd A. Greene, Columbia University Medical Center
Through its Center Grants Program, PDF supports groups of talented scientists, working on separate but related Parkinson’s projects, the flexibility necessary to collaborate and advance our understanding of Parkinson’s disease. In the current fiscal year, PDF is supporting Research Centers with $2.36 million — more than 50 percent of our total research budget.
Browse below for highlights of the work being done by each of our Research Centers - Columbia University Medical Center in New York; Rush University Medical Center in Chicago; and Weill Cornell Medical Center in New York.
The cornerstone of PDF's Center Grants Program is the program at Columbia University Medical Center in New York, NY. Since 1957, PDF has supported Columbia’s research efforts in finding the cause(s) of and a cure for Parkinson's.
Columbia's researchers and clinical doctors lead the field in research, training and impact in the study of Parkinson's disease. They 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.
Through PDF's support of Columbia’s post-graduate education and training programs, more than a hundred young scientists and Parkinson's specialists have been trained as Movement Disorder Fellows. Many of these former Fellows are today's leading investigators in the US and more than a dozen other countries.
With the modernization of the laboratories in the Black Building (a two-year project that was completed in early 2006) the research program has been significantly streamlined to increase efficiency and progress.
Recent grants have supported research in neuroinflammation, genetics, programmed cell death/GDNF in development of DA neurons, experimental animal models utilizing toxins and gene alterations, gene regulation in neuronal cell death, molecular alterations of nerve terminal dopamine pools, neuropsychology, behavioral effects, epidemiology, clinical trials and evaluation of surgical procedures.
A New Strategy for Neuroprotection in Parkinson’s Disease
In a new analysis of current Parkinson’s research, Robert E. Burke, M.D., and his colleagues at Columbia University, with funding from PDF, found that only about 30 percent of a person’s dopamine neurons have died by the time an individual is diagnosed with the disease. These new findings contrast with a widely cited number from previous studies that 50-70 percent or more of these cells have been lost at the time of diagnosis.
The motor symptoms of Parkinson’s are thought to develop when dopamine neurons die, but in Dr. Burke’s report, which appeared in the June 2010 issue of Annals of Neurology, he and his colleagues argued that it is more than simply
cell death that leads to the onset of Parkinson's. Instead, they point out, the development of Parkinson’s is also due to problems with communication, which takes place through the cells’ axons. Much like telephone lines downed by a powerful storm, the researchers say that Parkinson's is a storm that disrupts the proper communication of dopamine in the brain, causing Parkinson’s symptoms before nerve cells completely die.
The new hypothesis — that people newly diagnosed with Parkinson’s may have many more dopamine neurons than previously thought — provides grounds for optimism that therapies aimed at protecting these cells can be effective for treating Parkinson’s. It suggests the value of a new emphasis on neurorestoration therapies that would protect neurons by improving the health of axons. Restoring the health of axons may alleviate motor symptoms, prevent cell death, and, the authors say, possibly slow PD progression. The scientists caution that the field of understanding mechanisms of axon regeneration and the potential for axon regrowth is in its early stages.
Scientists Discover Key Process that Contributes to Common Form of Parkinson’s
Research led by Scott A. Small, M.D., of Columbia University with funding from PDF, has identified a molecular pathway — the polyamine pathway — that may explain how Parkinson’s develops in people who have no family history of the disease. Presented in the September 2010 issue of the Proceedings of the National Academy of Sciences, Dr. Small and his colleagues used a new technique called gene expression profiling to compare which genes were “switched” on or off in cells from two adjacent areas of the brain — one affected by PD, the other not. They found that a gene responsible for preventing the accumulation of a certain class of chemicals in the cell, called polyamines, was lower in those people who had Parkinson’s compared to those who did not.
The finding of an association between high polyamine levels and PD — if confirmed — may have two potentially important clinical implications. Since polyamines can be measured in blood and in cerebrospinal fluid, they may be used in tests for early detection of Parkinson’s or even for monitoring the effectiveness of future therapies. Currently, no such blood or spinal fluid tests are available. In addition, lowering polyamine levels in cells has been suggested by the authors as a novel approach to alter the course of Parkinson’s. Further research is needed to determine whether reducing polyamines may in fact ease Parkinson’s symptoms or slow disease progression.
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 through PDF’s Center Grant to Columbia University, 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.
In FY 2009, Weill-Cornell received $200,000 to support its research projects in Parkinson's disease.
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.
In FY 2009, the total PDF center funding - the PDF grant plus matching gifts - was $650,000. One half of this is contributed by PDF and the other half is provided as matching funds by Rush donors.
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.