NIH Extends Udall Grant Supporting Mayo Clinic's Parkinson's Research

NIH Extends Udall Grant Supporting Mayo Clinic's Parkinson's Research

Monday, February 11, 2013

JACKSONVILLE, Fla. — The National Institutes of Health has given Mayo Clinic in Florida a five-year, $7 million extension of its Udall Center of Excellence in Parkinson's Disease Research grant. NIH has continuously funded Mayo Clinic's Udall Center since 1999, shortly after President Bill Clinton signed the Morris K. Udall Parkinson's Disease Research Act into law.

There are only 10 Udall centers across the country investigating Parkinson's disease and other Parkinsonian disorders. In the United States, about 50,000 new cases of Parkinson's disease are diagnosed each year, adding to the 1 million people who currently have Parkinson's disease.

"The focus of Mayo's Udall Center is to understand genetic aspects of Parkinsonian disorders, and in this mission, we have made significant progress," says the center's director, neuropathologist Dennis Dickson, M.D. Dr. Dickson has led the center's brain banking efforts. The collection includes more than 1,000 brains, involving Parkinson's disease, progressive supranuclear palsy and multiple system atrophy. DNA from these brains has been invaluable in discovering genes that cause or are risk factors for Parkinsonian disorders.

"The NIH's grant extension recognizes Mayo's productivity, our unique resources, and the promise for further contributions," Dr. Dickson says.

The center brings together the disciplines of neurology, neurogenetics and neuropathology to discover new genetic causes of Parkinsonism, with the hope that these then lead to new disease models and eventual new treatments for Parkinsonism. Together, Mayo physicians and researchers have discovered a number of genes that cause Parkinsonian disorders, says neurologist Zbigniew Wszolek, M.D., an integral member of the research team.

For example, Mayo researchers:

    found the gene leucine-rich repeat kinase 2 (LRRK2) to be the most common genetic cause of late-onset, autosomal dominant Parkinson's disease;
    contributed to the discovery of mutations in the ±-synuclein gene (SNCA) that cause early-onset Parkinson's and identified genetic variants that are risk factors for the more common late-onset disease;
    dentified variants in a gene (EIF4G1) that is associated with Lewy body dementia;
    discovered mutations in a gene (DCTN1) that produces a very severe form of Parkinsonism associated with breathing difficulties and severe depression.

To date, researchers working at Mayo's Udall Center have identified 10 genes linked to Parkinson's disease or related neurodegenerative disorders, including frontotemporal dementia.

The Mayo Clinic Udall Center is known for its collaborative efforts to find and study families around the world who have different forms of early-onset, familial Parkinson's, the kind of Parkinson's significantly influenced by a mutated gene. Through Dr. Wszolek's work, the center has access to more than 850 families where more than one family member was affected by Parkinsonism.

"These studies offer clues to the most common kind of Parkinson's that occurs in the aged, which is believed to be caused by a mélange of genetic and environmental factors," Dr. Wszolek says. "The discovery of each gene opens the path to understanding the origins of the disease and for finding curative therapies."

Dr. Wszolek says progress in decoding Parkinson's genetic roots is accelerating. Until recently, every discovery was hard-won — researchers needed blood from several dozen affected members of a single family, and blood from hundreds of extended family members who were not affected by Parkinson's.

"Now we can do whole-genome screens using blood from three members of a family who have Parkinson's disease, and from two or three unaffected family members," he says.

Mayo's Udall Center collaborates with researchers in almost 30 countries and at 55 institutions, as well as with investigators at the other Mayo Clinic campuses in Rochester, Minn., and Scottsdale, Ariz.

Other key Udall researchers at Mayo include geneticists and molecular biologists Owen Ross, Ph.D., and Rosa Rademakers, Ph.D., and neurologists Ryan Uitti, M.D., and Jay Van Gerpen, M.D.

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