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Discovery of active genes reveals new clues on ALS

New England Journal of Medicine study supported by Augie's Quest offers increased opportunities for finding a cure

A University of California, Irvine neurologist is part of a national group of scientists who have identified the active genes in sporadic amyotrophic lateral sclerosis (ALS), a discovery that provides expanded opportunities for developing therapies to treat this chronic, incurable disease.

Led by researchers at the Translational Genomics Research Institute (TGen) in Phoenix, a comprehensive scan of the human genome has identified more than 50 genetic abnormalities in people with sporadic ALS, the most prevalent form of the disease. ALS also is known as Lou Gehrig’s disease.

Dr. Tahseen Mozaffar, a neurologist and director of the MDA ALS and Neuromuscular Diseases Center at the UC Irvine Medical Center, participated in the effort, which included a number of researchers from the Western ALS Group.

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Study results appear online in the New England Journal of Medicine. The study was supported by Augie’s Quest, a fast-track ALS research program, in conjunction with Muscular Dystrophy’s ALS Division.

Fitness pioneer Augie Nieto started Augie’s Quest after being diagnosed with ALS in March 2005. Nieto is co-founder and former president of Life Fitness, and chairman of Octane Fitness. He receives treatment at UC Irvine. Last year, Augie’s Quest donated $500,000 to UC Irvine’s MDA ALS and Neuromuscular Diseases Center. The grant is enhancing patient care services at the clinic and supports the activities of UC Irvine researchers who are seeking new therapies and a cure.

“This is a monumental step forward in the effort to find a cure for ALS,” Mozaffar said. “The genetics discovered in this study have uncovered a number of inviting targets for further study toward new drugs to treat this disease. And enthusiastic supporters like Augie Nieto and his wife Lynne are helping make this possible.”

The researchers also identified genes likely to play a role in cell function that controls nerve adhesion, offering a major new avenue for ALS research. The findings indicate these genes produce a sort of molecular glue that attaches motor neurons to muscle, according to Dietrich Stephan, TGen director of neurogenomics and the study’s principal investigator. It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die. TGen researchers identified the differences by screening DNA samples from more than 1,200 people with and 2,000 people without sporadic ALS.

ALS is a progressive neurological disorder that leads to paralysis and death, usually within three to five years. Sporadic ALS appears in 90 to 95 percent of all cases; the other 5 to 10 percent are the inherited form of ALS.

Mozaffar said that a mouse model of the inherited form of ALS is aiding research in that area. But no such model exists for sporadec ALS, making this finding critically important to advancing research in the most prevalent form of the disease.

Tom Vasich | EurekAlert!
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Further reports about: QUEST genes identified

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