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MDA-FUNDED SCIENTISTS FIND GENETIC
DIFFERENCES IN PEOPLE WITH ALS
TUCSON, Ariz., Aug. 1, 2007 - Scientists at the Translational Genomics Research Institute (TGen) in Phoenix have identified changes in 41 genes in people who have the sporadic (not inherited) form of amyotrophic lateral sclerosis (ALS), the Muscular Dystrophy Association announced today.

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

“The majority of cases of ALS seem to happen ‘out of the blue,’” said Sharon Hesterlee, Vice President of Translational Research at MDA. “It’s likely that genetics play some role in a person’s susceptibility to the disease, and this type of study may be our best bet for learning about the genetic contribution.”

Dietrich Stephan, director of TGen’s Neurogenomics Division, and colleagues at TGen published their findings in today’s issue of the New England Journal of Medicine, in collaboration with scientists at several academic institutions.

Using state-of-the-art technology, the investigators scanned for differences in the entire genome (complete set of genes) from 1,200 people with and 2,000 people without sporadic ALS, which accounts for 90 percent of cases.

Results showed statistically significant differences between the ALS-affected and unaffected study participants’ DNA near 41 genes.

One location was significantly different in the two sets of samples even after an extremely conservative statistical procedure was applied to rule out any possible coincidences in the data.

The function of the gene associated with this leading difference isn’t yet known, the researchers say, but several of the others point to the involvement of various biological pathways in ALS, only some of which were previously considered.

The known functions of genes at many of the identified locations suggest that variant forms of proteins involved in the structure of the cellular scaffolding, in the stickiness of structures at the junction of nerve and muscle cells, and in inflammation may play a role in ALS suceptibility.

Hesterlee noted that MDA will fund additional studies to follow up on these initial findings and see whether the DNA variations can actually cause the type of biological changes seen in ALS. She also said she would like to see the findings replicated in larger numbers of people.

The project was funded by a $652,000 grant from MDA’s Augie’s Quest, a fast-track ALS research initiative, in collabortaion with TGen. Blood 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 other sites across the country.

The scientists used gene chips, also known as microarrays, manufactured by Affymetrix of Santa Clara, Calif., to carry out the work. Gene chips are designed to allow computer software to detect minute differences among DNA sequences.


About MDA
MDA (www.mda.org) is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services and far-reaching professional and public health education. It maintains 225 neuromuscular disease clinics across the United States.
This year, MDA will spend some $13 million on ALS research and another $10 million for ALS services. Since its inception, the Association's expenditures for ALS research and services have exceeded $210 million.


About Augie's Quest
Fitness pioneer Augie Nieto started Augie's Quest (www.augiesquest.org) in conjunction with MDA's ALS Division. Nieto is co-founder and former president of Life Fitness, and chairman of Octane Fitness. He and his wife, Lynne, serve as co-chairpersons of MDA's ALS Division. Nieto received a diagnosis of ALS in March 2005.


About TGen
TGen (www.tgen.org) is a nonprofit organization focused on developing earlier diagnostics and smarter treatments. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen's research is based on personalized medicine. The institute plans to accomplish its goals through robust and disease-focused research.


About Affymetrix Inc.
Affymetrix Inc. (www.affymetrix.com) scientists invented the world’s first high-density microarray in 1989 and began selling the first commercial microarray in 1994. The microarray technology is used by the world’s top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and nonprofit research institutes.


http://www.als-mda.org/research/news...fferences.html