April 26, 2007

RESEARCHERS FIND NEW EVIDENCE FOR IMMUNE-SYSTEM INVOLVEMENT IN ALS

TUCSON, Ariz., April 26, 2007 - Researchers in the laboratory of Don Cleveland at the University of California-San Diego have added to a growing body of evidence that implicates the immune system in amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), the Muscular Dystrophy Association announced today. The team, which included MDA-supported Severine Boillee, says the findings could have important implications for therapy development.

"Every bit of information we learn about this disease is a step toward identifying targets for new drugs," said Sharon Hesterlee, MDA's vice president of Translational Research.

ALS is a progressive disease of the motor neurons, nerve cells that send signals to muscles. It causes paralysis of all voluntary muscles, usually resulting in death from respiratory paralysis in three to five years. The cause of the vast majority of cases is unknown, although the cause of some genetic forms is well understood.

The researchers, who will publish their complete findings online April 27 in Proceedings of the National Academy of Sciences (but released preliminary findings April 16), found that mouse motor neurons carrying mutated genes known to cause ALS make proteins that are part of the immune system's "classic complement pathway." These proteins then signal neighboring immune-system cells called microglia, which may attack and kill the motor neurons. The data imply that therapies that interfere with the complement pathway or with microglial activation would likely be beneficial in ALS.

Although it isn't known whether these findings apply to nongenetic forms of ALS, there is evidence to suggest that these two major forms of the disease differ only at the very beginning and quickly converge.

The new findings come on the heels of reports released earlier this month showing that an as-yet-unidentified substance released from non-nerve cells is highly toxic to nearby motor neurons. This compound is released from cells called astrocytes, which are not the same as microglia and are not part of the immune system.

Both sets of findings have important implications if stem cell therapies are to be attempted to treat ALS.

"It's now clear that in inherited ALS the neurons are genetically damaged and start making proteins normally made by immune cells," Cleveland said. "But ALS is not just a disease of motor neurons. Neighboring cells are key to disease progression. These non-neuronal cells initially respond to the injured neurons, but when they're damaged themselves, they turn them into clumsy, unfriendly neighbors whose action actually accelerates disease progression. One implication of this is that stem cell therapies to replace the damaged neighbors may be a very effective approach for slowing disease progression."

About MDA

MDA (www.mda.org) is the world's largest provider of ALS services and funder of ALS research, having expended $200 million. It operates 225 neuromuscular disease clinics across the country and 37 ALS-specific research and care centers.