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 Parkinsonís 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 Parkinsonís 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 Parkinsonís
disease and related neurodegenerative disorders.
"Recent progress in Parkinsonís 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 Emoryís 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 Parkinsonís disease. The Emory scientists will also study the utility of deep brain
stimulation, in both animal models and patients, as a treatment for Parkinsonís disease. The Emory Center will attempt to refine
our knowledge of the functional changes that accompany Parkinsonís disease using several different techniques. Investigators
there plan to develop a new rodent model with chronic neurodegenerative symptoms similar to Parkinsonís. Current animal
models have acute disease and do not mimic the slow progression seen in people with Parkinsonís. 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
Ted M. Dawson, M.D., a well-respected authority on movement disorders and director of the Parkinsonís Disease Center at
The Johns Hopkins University School of Medicine in Baltimore, Maryland, will direct the Parkinsonís Disease Research Center
of Excellence there. His group will be studying a family of proteins known as synucleins in tissue cultures, animal models of
Parkinsonís, and patients with the disease. Synucleins, and particularly the gene for alpha-synuclein, have been implicated in the
development of several neurodegenerative diseases, including Parkinsonís and Alzheimerís. 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 Parkinsonís 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 Parkinsonís disease. They will examine the roles that the genes for three
proteinsóalpha-synuclein, parkin, and torsinAóplay in the death of nerve cells. Such studies will help define which genetic
traits contribute to an individualís susceptibility to Parkinsonís. 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 Parkinsonís.
"These grants represent a significant escalation in the war to overcome Parkinsonís 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 Parkinsonís 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.