Boston-led team discovers new ALS gene

A research group led by Boston scientists has found a gene whose defects cause a familial form of ALS, the devastating neurological disorder better known as Lou Gehrig's disease.

Ten percent of amyotrophic lateral sclerosis cases are inherited. The disease has been traced to only a few gene mutations that lead to the death of nerve cells that send messages to muscles. Most people develop ALS in middle age, becoming progressively weaker and then paralyzed, usually dying of respiratory failure within two to five years. About 30,000 Americans have the disease, according to the ALS Association.

A team from Massachusetts General Hospital, the Broad Institute, MIT, and other institutions write in tomorrow's Science about their discovery of a fourth gene whose 13 mutations caused ALS in a family of Cape Verdean origin. In another Science paper, a group in England reports two more mutations in the same gene that were found in eight British families.

"Every time a new gene like this is found, it illuminates a new pathway for triggering the disease," senior author Dr. Robert H. Brown Jr. said in an interview. "Once one has the gene, one can make a mouse model or cell model for this disease, which should accelerate efforts to find therapies for it."

While he was at Mass. General and Harvard Medical School, Brown found the first gene linked to familial ALS in 1993. He moved to the University of Massachusetts Medical School in October, after the work reported in Science was completed.

The Boston researchers found the new gene mutations by sequencing the genes of a family from the Cape Verde Islands. Looking at genes on a chromosome that previous research had hinted might be important in ALS, they detected mutated versions of one gene in four family members who had developed ALS and in three relatives younger than the typical age for onset of ALS who had no symptoms. None of the gene mutations was found in samples taken from 1,446 North Americans as a comparison.

Now the scientists are trying to understand how the mutations lead to ALS. The answer could have a bearing on the more common, non-familial form of ALS and perhaps other neurological disorders.

"These findings will open up a completely new avenue of investigation with the potential of developing more promising therapies for ALS," Lucie Bruijn of the ALS Association said in a statement.

The ALS Association and other disease advocacy groups provided support for the study, which was also funded by a grant from the National Institutes of Health.