Three top university hospitals will receive a total of almost $24 million from the National Institute of Neurological Disorders and Stroke (NINDS) to advance understanding of Parkinson's disease and related movement disorders. Investigators at Emory University, Massachusetts General Hospital, and The Johns Hopkins University School of Medicine will spend the next five years unraveling the cause or causes of Parkinson's disease and seeking new ways to diagnose and treat it. They will also provide state-of-the-art, multidisciplinary training for young scientists preparing for research careers investigating Parkinson's disease and related neurodegenerative disorders.
"Recent progress in Parkinson's research is creating extraordinary opportunities for increasing our knowledge of the fundamental processes underlying this debilitating disease," says Gerald Fischbach, M.D., director of the NINDS. "We must maximize our efforts to take advantage of these opportunities. Multidisciplinary centers such as these are in an excellent position to exploit emerging basic findings and new technological developments that demand collaborative efforts if they are to evolve into clinical breakthroughs."
In Atlanta, Georgia, the research team will be led by Emory's Chairman of Neurology, Mahlon R. DeLong, M.D. A leading international authority on movement disorders, Dr. DeLong played a seminal role in the development of pallidotomy, a surgical technique showing promise as a treatment for Parkinson's disease. The Emory scientists will also study the utility of deep brain stimulation, in both animal models and patients, as a treatment for Parkinson's disease. The Emory Center will attempt to refine our knowledge of the functional changes that accompany Parkinson's disease using several different techniques. Investigators there plan to develop a new rodent model with chronic neurodegenerative symptoms similar to Parkinson's. Current animal models have acute disease and do not mimic the slow progression seen in people with Parkinson's. Such a model would not only assist investigators in their studies of the brain pathways involved in the disorder, but would also allow testing of potential therapies in a system more closely resembling human disease. In addition, the role of selected receptors (proteins on the surface of a cell that allow the cell to identify foreign structures) will be studied to determine which may be the best candidates for therapeutic interventions.
Ted M. Dawson, M.D., a well-respected authority on movement disorders and director of the Parkinson's Disease Center at The Johns Hopkins University School of Medicine in Baltimore, Maryland, will direct the Parkinson's Disease Research Center of Excellence there. His group will be studying a family of proteins known as synucleins in tissue cultures, animal models of Parkinson's, and patients with the disease. Synucleins, and particularly the gene for alpha-synuclein, have been implicated in the development of several neurodegenerative diseases, including Parkinson's and Alzheimer's. The investigators will explore the relationship of synucleins to both cognitive impairment and oxidative stress, a process thought to cause damage to nerve cells. Another substance being studied by the Hopkins group for its potential neurotoxicity is nitric oxide. The scientists will also attempt to develop a cellular model of Parkinson's disease in which to study both the pathways leading to cell death and the effects of experimental therapies.
John B. Penney, Jr., M.D., will oversee the Massachusetts General Hospital team in Boston. Dr. Penney has an outstanding background in the field of neurodegenerative diseases and has published extensively on movement disorders research. His group will focus on the genetics of Parkinson's disease. They will examine the roles that the genes for three proteins --alpha-synuclein, parkin, and torsinA-- play in the death of nerve cells. Such studies will help define which genetic traits contribute to an individual's susceptibility to Parkinson's. Mice with mutated alpha-synuclein and parkin genes will be studied for behavioral and neurophysiological effects. These investigations, done in collaboration with scientists at the Massachusetts Institute of Technology, could yield significant improvements in the diagnosis and treatment of Parkinson's.
"These grants represent a significant escalation in the war to overcome Parkinson's disease," says Dr. Fischbach. "We hope to make additional awards next year."
More than half a million Americans have Parkinson's disease, a neurological disorder of later life, that progressively impairs control of body movement, interferes with such abilities as walking and talking, and often leads, over time, to rigid immobility. Symptoms of Parkinson's disease include tremor (particularly tremor of a body part at rest), stiff limbs, slow or absent movement, lack of facial expression, a shuffling gait, and a distinctive stoop. Other symptoms, such as depression and impaired ability to think, may also develop, especially during the later stages of the disease. These symptoms result from degeneration of nerve cells in the brain, particularly those involved in the production of the chemical dopamine. Although standard treatment with the drug combination levodopa/carbidopa can restore virtually normal movement to many people with Parkinson's early in the disease's course, the treatment loses effectiveness as the disease progresses. The withered cells fail to release dopamine, one of the neurotransmitters, or nerve-signaling chemicals, crucial for communication between nerve cells.
The NINDS, one of the National Institutes of Health located in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain.