Michael J. Fox Foundation grant awarded to UCSD Parkinson's researcher

June 21, 2001

The Michael J. Fox Foundation for Parkinson's Research has awarded one of its first-ever grants to UCSD for studies of a naturally occurring protein that has potential as a new Parkinson's disease therapy.

Eliezer Masliah, M.D., UCSD professor of neurosciences and pathology, received one of 15 $100,000 grants awarded by the Fox Foundation to researchers pursuing a cure for the debilitating neurological disorder that affects 1.5 million Americans and one in 100 adults over age 60.

Studies have shown that abnormal accumulation of proteins called alpha-synuclein (a-synuclein) are centrally involved in Parkinson's disease. A-synuclein is a major component of Lewy bodies, which are an abnormal dense mass of proteins called aggregates, found in the dying neuron cells of Parkinson's patients.

Masliah's lab was the first to identify and clone human a-synuclein in 1991. When mutations occur in a-synuclein, or when environmental toxins trigger changes in its characteristics, the protein aggregates, or forms Lewy body clogs within the brain.

Recently, Masliah's team identified a protein similar to a-synuclein, but with the ability to block the development of Lewy bodies, rather than form them. Called beta-synuclein (b-synuclein), this naturally occurring protein was first studied in test tubes. Scientists added b-synuclein to a-synuclein protein that had formed aggregates, and watched as the aggregates untangled. In preliminary animal studies, Masliah developed one group of mice with over-expressed a-synuclein and another group with large amounts of b-synuclein. The a-synuclein mice developed Lewy bodies in their brains while the b-synuclein group did not. When the two groups were crossbred, their offspring were protected from developing brain Lewy bodies.

Over the next six months, studies in mice will continue, Masliah says. The researchers have identified the portion of the b-synuclein molecule that blocks aggregation and are investigating the development of a way to deliver b-synuclein by gene therapy into the brain. They are also trying to develop a chemical compound structurally similar to the naturally occurring b-synuclein protein. Theoretically, the chemical compound could be taken as oral medication to untangle Lewy bodies in the brain. Both of these methods will be tested over the next months to years in mice.

The recently formed Michael J. Fox Foundation for Parkinson's Research raised $1.5 million for its first round of grants. The organization's literature notes that it has moved "aggressively to identify the most promising research and raise the funds to assure that the best research is supported..."

Additional institutions receiving the first Fox Foundation grants were Harvard's Brigham and Women's Hospital, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, Rutgers University, Baylor College of Medicine, Rush University, European Molecular Biology Laboratory, University of Toronto, University of Florida College of Medicine, Clinica Universitaria de Navarra, Zygogen LLc, University of Minnesota, University of Medicine and Dentistry of New Jersey, and University of Pittsburgh School of Medicine.

University of California - San Diego

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