The ALS Association

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Carrie Munk
The ALS Association
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New Discovery of Normal Function of ALS Gene Will Aid Drug Development to Slow or Stop Disease

Washington, D.C. (March 18, 2016)— Mutations in the C9orf72 gene are known to be the most common genetic cause of ALS. According to new research, C9orf72 is important for immune system function in its normal form, an important discovery made by scientists Jacqueline O’Rourke, Ph.D., and Robert Baloh, M.D., of Cedars-Sinai Medical Center in Los Angeles, that is likely to influence the development of treatments aimed at silencing the C9orf72 mutant gene. The findings were published today in the journal Science.

ALS is a progressive neurodegenerative disease that affects 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. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.

Mutations in the C9orf72 gene are responsible for up to 40 percent of familial ALS cases and 6 percent of sporadic cases, as well as a fraction of cases of frontotemporal dementia. The mutation causes production of excess RNA, which is believed to contribute to disease through multiple mechanisms. Despite progress in understanding these mechanisms, it has remained unclear what the normal function of the gene is and whether any part of the ALS disease process is due to loss of function, rather than gain of new toxic functions from the mutant gene.

In the current study, first author Jacqueline O’Rourke, Ph.D. and team investigated the normal function of the C9orf72 gene in mice completely lacking the mouse equivalent of this gene. The mice developed normally and showed no signs of motor neuron death, confirming that loss of gene function is not the primary cause of loss of motor neurons in the human disease. Instead, the team found that immune system cells in the spleen and elsewhere called macrophages, as well as immune cells in the brain called microglia, displayed serious abnormalities in structure and function, consistent with disruption of the pathways that degrade and recycle cell components. In ALS, the team suggested, loss of this function may contribute to the neuroinflammation seen in the brain that contributes to the disease process.

“The results of this study shed light on the normal function of the C9orf72 gene,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “Antisense therapies to silence mutant C9orf72 are currently one of the most promising treatment strategies for this form of the disease. This data emphasizes the importance of avoiding silencing the normal gene in the development of this treatment approach. Lowering the mutant protein may have impact on the inflammatory response related to the disease.”

About The ALS Association
The ALS Association is the only national non-profit organization fighting Lou Gehrig’s Disease on every front.  By leading the way in global research, providing assistance for people with ALS through a nationwide network of chapters, coordinating multidisciplinary care through certified clinical care centers, and fostering government partnerships, The Association builds hope and enhances quality of life while aggressively searching for new treatments and a cure.  For more information about The ALS Association, visit our website at

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