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School of Medicine: Morris K. Udall Parkinson’s Disease Center of Excellence
September 18, 2007, Volume 54, No. 4

The University of Pennsylvania School of Medicine will receive $1.5 million annually from the National Institute of Neurological Disorders and Stroke (NINDS) over the next five years to study the molecular mechanisms that underlie the cognitive and movement aspects of Parkinson’s disease, as well as enhance the care and treatment of patients and training of physicians. The Penn Udall Center is the only center to focus on dementia and Parkinson’s disease.

Parkinson’s is one of the most common neurodegenerative diseases, second only to Alzheimer’s disease in the number of people affected. Estimates suggest that approximately 750,000 Americans have Parkinson’s.

“This grant will enable us to better leverage our achievements in clinical care for Parkinson’s patients with our strong background in research on the basic sciences behind neurological disorders,” said Center Director Dr. John Trojanowski, director of Penn’s Institute on Aging. “The theme of the Udall grant is cognitive impairment, a very much neglected aspect of Parkinson’s disease. This grant will bring together movement disorder physicians with experts in cognition and neuropsychiatry.”

“NINDS funding will help us build on our existing Parkinson’s efforts as well as recruit new faculty to the research program,” said Dr. Arthur Rubenstein, EVP of the University of Pennsylvania for the Health System and Dean of the School of Medicine. “The award is a testament to the characteristic collegiality and team approach to science at Penn. This award will further add to our international reputation for multidisciplinary research excellence in neurodegenerative diseases of aging.”

The Penn Udall Center is based on 20 years of basic research on neurodegenerative diseases within the Center for Neurodegenerative Disease Research and clinical programs at the Parkinson’s Disease and Movement Disorder Center, both within the UPHS.

Dr. Trojanowski will coordinate the Center’s overall operations and conduct neuropathology and genetics research. Dr. Howard Hurtig, will investigate potential markers of Parkinson’s-related neurodegeneration, as well as lead educational efforts for physicians and the lay community. Dr. Andrew Siderowf, and Dr. Murray Grossman, will help mark out the nature of cognitive impairments in Parkinson patients. Dr. Virginia M.-Y. Lee and Dr. Benoit Giasson, will study the nature of these impairments in mouse models. Dr. Sharon Xie, will oversee data management and biostatistics for the initiative.

The Udall Centers of Excellence were developed in honor of former Congressman Morris K. Udall, who died in 1998 after a long battle with Parkinson’s disease. The first center was named in 1997. Joining the existing 13 Centers, the Penn Udall Center has several objectives:

• Develop a new rating scale of activities of daily living for Parkinson’s patients to distinguish between cognitive and motor impairments.
• Investigate the neural basis of cognitive deficits in Parkinson’s disease, using MRI, among other techniques.
• Conduct studies with animal models of Parkinson’s disease to elucidate the role of alpha-synuclein proteins in disease pathology.
• Study the role of protein aggregations in Parkinson’s dementia pathology.

“Most significantly, advances in understanding how the accumulation of nerve-cell debris formed by the Lewy body protein alpha-synuclein causes motor and cognitive impairments in Parkinson’s disease are leading to the identification of exciting new targets for drug discovery aimed at stopping or slowing Parkinson’s,” said Dr. Trojanowski. “The Parkinson’s brain is flooded with deposits of alpha-synuclein misfolded protein and understanding how this happens suggests several novel therapies.”

One approach is to unclog the normal protein disposal mechanisms in sick nerve cells so pathological alpha-synuclein is cleared and no longer accumulates. This strategy will prevent sick nerve cells from being damaged by the alpha-synuclein debris. Alternatively, reducing the amount of pathological alpha-synuclein in sick nerve cells will help the normal disposal mechanisms in the brain to work effectively. “These success stories from the lab offer real hope for better patient therapies to stop or slow the progression of Parkinson’s,” Dr. Trojanowski said of the new Center’s overall aim.

Almanac - September 18, 2007, Volume 54, No. 4