A discovery in a tiny roundworm may pave the way for the development of a drug that will cure or slow the progression of amyotrophic lateral sclerosis (ALS), a devastating disease also known as Lou Gehrig's disease. The breakthrough may also be a new approach to treatments for other neurodegenerative diseases such Alzheimer's, Parkinson's, and Huntington's.

Researchers at CHUM Research Center and the University of Montreal found that the immune system in a 1 mm-long roundworm is critical to the development of ALS. "An imbalance of the immune system can contribute to the destruction of motor neurons and trigger the disease," said Alex Parker, CHUM researcher and associate professor in the Department of Neuroscience at the University of Montreal.

ALS is a neuromuscular disease that attacks neurons and the spinal cord. Patients gradually become paralyzed, and usually die within five years. There's no cure, and the only medication approved to treat the disease, riluzole, only extends the patient's life by a few months.

More than a dozen genes related to ALS have already been discovered, and a mutation in only one causes the disease.

In the current study, scientists inserted a mutated human gene into C. elegans, a nematode worm used for genetic experiments. Within 10 days, the worms were paralyzed. "The worm thinks it has a viral or bacterial infection and launches an immune response. But the reaction is toxic and destroys the animal's motor neurons," said Parker.

Scientists then modified another gene — tir 1— that plays an important role in the immune system. Results were significant: The worms with the gene mutation suffered far less paralysis.

The same process probably also works in people, say the researchers, who have found that the human equivalent of the tir-1 gene — SARM1 — is crucial to proper functioning of the immune system.

The signaling pathway is identical for all genes associated with ALS in humans. Therefore, the SARM1 gene makes an excellent target for future medications, because it is a part of a process that turns cellular function on and off, and can be blocked by existing drugs.

Parker and his team are already testing FDA-approved drugs to treat disorders such as rheumatoid arthritis, to see if they will treat ALS.

There are still obstacles to be overcome. "In our studies with worms, we know the animal is sick because we caused the disease," Parker said. "This allows us to administer treatment very early in the worm's life. But ALS is a disease of aging, which usually appears in humans around the age of 55. We do not know if a potential medication will prove effective if it is only given after appearance of symptoms. But we have clearly demonstrated that blocking this key protein curbs the disease's progress in this worm."

The study was published in Nature Communications.