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."
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, Sciencexpress online