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Thursday, November 30, 2006

Scan of Human Genome Finds Unexpected Clues on Lou Gehrig's Disease

A comprehensive scan of the human genome has identified more than 50 genetic abnormalities in people with sporadic amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), the Muscular Dystrophy Association (MDA) and the Translational Genomics Research Institute (TGEN) have announced. The most common of these abnormalities have never before been shown to play a role in the disease.

TGen researchers, announcing the findings at an international ALS conference in Japan, said the identified differences implicate genes likely to play a role in cell function that controls nerve adhesion, offering a major new avenue for ALS research. TGen researchers identified the differences by screening DNA samples from over 1,200 people with and 2,000 people without sporadic ALS using state-of-the-art microarray technology by Affymetrix of Santa Clara, Calif.

"Our findings indicate these genes produce a sort of molecular glue that attaches motor neurons to muscle. It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die," says Dietrich Stephan, TGen director of Neurogenomics and the study's principal investigator.

ALS is a progressive neurological disorder that leads to paralysis and death in three to five years. It has baffled researchers for nearly 140 years.

What is extraordinary about this study is how quickly this breakthrough occurred. A new fast-track research funding approach used by MDA and a new microarray technology by Affymetrix that lets researchers quickly scan people's genomes enabled the experiment to be completed in just nine months.

"There is a revolution going on in research, and this study is a perfect example of how things are changing," says Sharon Hesterlee, MDA vice president of translational research. "New technology is letting us look at the genome at a level of detail that was unthinkable just a few years ago and, as a result, costs are coming down, results are coming much faster and we're seeing breakthroughs in diseases that have baffled researchers for decades."

The Affymetrix 500K Arrays identified the genetic differences between the affected and unaffected groups and rapidly produced a genetic map of each individual.

"Just a couple of years ago, this experiment would not have been possible because there simply wasn't a technology that enabled scientists to sift through the three billion molecules in the genome to find the genetic abnormalities that cause disease," says Sean George, vice president Academic Business Unit at Affymetrix. "The 500K microarray used on this experiment employs the same kind of semi-conductor technology that powers super computers."

According to MDA and TGen, the next steps center around high- throughput screening for drugs that act on the biochemical pathways identified by the DNA screen.

The massive project was funded by a $652,000 grant from MDA's Augie's Quest, a fast-track ALS research program, in collaboration with TGen. Blood donated for the study came from the MDA/ALS Center at Methodist Neurological Institute in Houston, the Forbes Norris MDA/ALS Center at California Pacific Medical Center in San Francisco, the MDA/ALS Center at the University of Pittsburgh, and the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York, as well as a dozen other collection sites throughout the United States.

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