New Gene for Lou Gehrig's Disease Identified

"I think it's a very, very exciting finding," Lee said, especially in light of the recent publication in theAnnals of Neurologyof another case of familial ALS with a mutation in TDP-43.

Dr. Catherine Lomen-Hoerth, director of the ALS Center at the University of California, San Francisco, said the findings could aid ALS research and drug development.

"For a long time, we've only had one good genetic mouse model for the disease," she said, referring to the SOD1-based model. "I think this discovery provides the possibility of making a mouse model that might be very helpful to help understand both ALS and FTLD."

The two diseases "may represent opposite ends of a spectrum of the same disease," Lee explained.

Most ALS cases (except those caused by SOD1 mutations) exhibit TDP-43 accumulations, Shaw said. Yet mutations in the gene appear to be relatively rare, at least based on their prevalence in the current study. What these latest findings do is provide "the first concrete link" between TDP-43 and disease pathology.

The situation is analogous to Alzheimer's disease, he said, which is associated with beta-amyloid protein accumulation. Though relatively few Alzheimer's cases are actually caused by mutations in the amyloid protein gene, their discovery underscored the protein's role in disease pathology.

"It gives us a biochemical tool to recapitulate the disease process in animals, to begin to develop treatments," Shaw said. "And so, it is a really crucial weapon against the disease."

More information

For more on amyotrophic lateral sclerosis, visit the ALS Association.

SOURCES: Christopher Shaw, M.D., Ph.D., professor, neurology and neurogenetics, King's College London; Catherine Lomen-Hoerth, M.D., Ph.D., associate professor, neurology, and director, ALS Center, University of California, San Francisco; Virginia Lee, Ph.D., professor, pathology & laboratory medicine, University of Pennsylvania School of Medicine, Philadelphia; Feb. 28, 2008,Sciencexpressonline