Genetic clues to ALS
Researchers report several gene variants have been linked to the presence of Lou Gehrig's disease

BLOOMBERG NEWS
August 24, 2007

Scientists have linked gene variants to amyotrophic lateral sclerosis, the incurable nerve disorder that paralyzed and killed baseball's Lou Gehrig.

One of the genes linked to ALS, often called Lou Gehrig's disease, makes a protein that appears to poison muscle-stimulating nerve cells in laboratory dishes, said Dietrich A. Stephan, director of discovery research at the Translational Genomics Research Institute in Phoenix, who led the study.

The gene, called FLJ10986, along with at least 10 others identified in the study, may shed light on a disease that strikes about one in 17,000 people and has puzzled scientists for decades. Clues as to how the disorder causes nerves to disconnect and pull away from muscles may help doctors devise new treatments within a few years, Stephan said.



"As we unravel the biology, there's a good chance that we could stop the progression of the disease," he said yesterday in a telephone interview. "We may potentially even get the nerve cell bodies to reconnect to muscles."

A form of ALS that runs in families is closely linked to abnormalities in a gene called SOD1 that makes a nerve cell toxin called superoxide dismutase. For more than 90 percent of cases, studies have implicated a few muscle proteins that appear to be associated with the disease.

Stephan led a nationwide team of researchers at U.S. medical schools, hospitals and research centers in the effort to compare DNA from 1,251 ALS patients with samples from about 1,500 healthy people. They used research tools that allowed them to detect variations at more than 700,000 points in each DNA sample.

Stephan started by comparing DNA from 386 patients and 546 people without the disease. People with ALS were 35 percent more likely to have the FLJ10986 gene than those without the malady, according to the study, published today in the New England Journal of Medicine.

The role of the protein "is definitely worth following up on," said Kari Stefansson, chief executive of Decode Genetics Inc., the Icelandic company that develops drugs by finding disease-associated genes. "I think we need a lot more work in this area, and since we have failed with all other methods, genetics is something we need to put more resources into."

The researchers performed the same test in two other groups of patients and found at least 10 more genes with relatively strong links to ALS, the study said. All of them should be more thoroughly investigated to see whether they can help explain ALS, Stephan said.

The study was supported by a grant from the Muscular Dystrophy Association in Tucson and the Dorrance Family Foundation in Scottsdale, Ariz.

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