New research implicates that RNA processing is central to ALS disease process

In work supported by The ALS Association, researchers have discovered a new ALS-causing gene and have linked its function to that of another prominent disease gene. The study was published in the journal Nature Neuroscience.

ALS (amyotrophic lateral sclerosis), otherwise known as Lou Gehrig's Disease, is a progressive neurodegenerative disease that affects neurons (nerve cells) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure and no life-prolonging treatments for the disease. 

Mutations in the gene, called MATR3, were discovered in a family with members who were affected by ALS and dementia. The investigators subsequently identified similar mutations in an additional family, out of 108 familial cases tested. It was also found in one individual with sporadic ALS, out of 96 tested.

The authors showed that the MATR3 protein, called matrin, interacts with TDP-43, also a cause of ALS. TDP-43 aggregates inside cells in most people with ALS and mutant matrin was found to co-aggregate with it in the muscles of one person studied. Like TDP-43, matrin binds to DNA and to RNA and is normally involved in processing genetic messages.

The research was performed by an international team under the leadership of Bryan Traynor, M.D., Ph.D., of the National Institute on Aging, and Adriano Chio, M.D., of the University of Turin, Italy. Their research is directly supported by The ALS Association. Exome sequencing data on all individuals in this study are being made available in a public database so that other researchers can learn more about this mutation.

"We are very excited by this finding. It provides fresh insight into the pathogenesis of ALS and further implicates RNA metabolism as central to the death of motor neurons," said Dr. Traynor. "There has been tremendous progress in recent years, and we now know the genetic etiology of about two-thirds of familial ALS cases and approximately 10 percent of sporadic ALS cases. Nevertheless, there are still many more genes to find."

"This is an exciting and potentially very important discovery," said Lucie Bruijn, Ph.D., MBA, Chief Scientist for The Association. "It strengthens our belief that RNA processing is central to the ALS disease process, and it provides another clue that TDP-43 is one of the hubs of that process. These discoveries will help us better understand how the normal function of motor neurons is perturbed in the disease and allow us to think about new routes for therapies to restore that function."

SOURCE The ALS Association