Lou Gehrig’s disease gene discovered

Apr 29 2004

A gene for a rare juvenile-onset form of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) has been isolated in families in the United States, Belgium and Austria, the Muscular Dystrophy Association (MDA) announced today.

The gene, which carries instruction for a protein called senataxin, normally helps the cell interpret and process genetic instructions along the biochemical pathway from DNA to protein manufacturing. When senataxin is flawed, as it is in these ALS-affected families, this pathway is apparently disrupted, leading to the gradual death of muscle-controlling nerve cells in the brain and spinal cord (motor neurons).

“This discovery fills in one more piece in the puzzle of the causes of ALS,” said neurologist Valerie Cwik, MDA’s medical director. “It also provides a new line of investigation for the development of treatments for this devastating disease.”

The senataxin finding, though it explains only a small percentage of ALS cases, may have implications for the larger world of ALS.

Most cases of ALS aren’t clearly genetic, begin in late middle age, and progress rapidly to paralysis and death.

MDA grantee Phillip Chance, professor of neurology and pediatrics at the University of Washington in Seattle, led the international team, which pooled DNA samples from the three countries. He said the senataxin finding might have more widespread implications than those immediately apparent.

“Given that mutations in senataxin associated with ALS4 lead to motor neuron degeneration, a shared disease mechanism in all forms of ALS, both juvenile and adult-onset types, might exist,” Chance said.

MDA grantee Craig Bennett, research assistant professor of pediatrics at the University of Washington, agreed.

“We hypothesize that common pathways may involve defects in RNA (a chemical cousin of DNA) processing in motor neurons. Such questions may be addressed and answered in systematic research studies,” Bennett said.

In 1993, another MDA-funded team identified defects in a chromosome 21 gene known as SOD1 as one cause of adult-onset ALS. The mechanisms by which SOD1 flaws kill motor neurons are still under study, and mice with flawed SOD1 genes have provided what may be the most important research tool the ALS community has had to date.

The finding was published online by the American Journal of Human Genetics.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases, including ALS, through programs of worldwide research, comprehensive services, and far-reaching professional and public health education. MDA is the world’s largest nongovernmental sponsor of ALS research and services.