The ALS Association

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Carrie Munk
The ALS Association
(571) 319-3047



New ALS Model Argues for Early Treatment

Washington, D.C. (December 2, 2015) — Results from two independent research groups on an important new mouse model of inherited ALS gene C9orf72 indicate that development of disease pathology precedes neurodegeneration, and can be reversed by therapies targeting the mutant gene responsible for the pathology. The studies were funded in part by The ALS Association.

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 the most common cause of inherited ALS and frontotemporal dementia. Previous work in cell culture and invertebrate models, as well as study of patient tissue, has shown that the mutation causes two major pathologic changes: aggregation of RNA transcripts from the mutated gene, and production of so-called dipeptide repeat proteins (DPRs). Evidence has accumulated that both forms of pathology may lead to disease progression.

The two new studies were led by Jacqueline O’Rourke, Ph.D., and Robert Baloh, M.D., Ph.D., both of Cedars-Sinai Medical Center in Los Angeles, and Owen Peters, Ph.D., Gabriela Toro Cabrera, and Robert Brown, M.D., of the University of Massachusetts Medical Center in Worcester. Both groups created a new model of C9orf72 disease by inserting the gene carrying a large number of the expanded repeats into mice using a bacterial artificial chromosome, a genetic engineering tool specialized for carrying very large pieces of DNA. In both studies, mice carrying the gene developed both RNA aggregates and DPRs, but, showed no signs of neurodegeneration, even at an advanced age. The results suggest that additional factors may be needed to cause neurodegeneration, the authors concluded.

Dr. Baloh and colleagues showed that treatment of mouse-derived cell lines with an “antisense” RNA against the mutant gene could suppress production of both forms of pathology. Dr. Brown and colleagues targeted the mutant gene with a “micro RNA” delivered by a gene therapy vector, which also reduced the two pathological products of the mutant gene.

“These two studies use an important new model of ALS to explore the critical question of how the C9orf72 mutation leads to disease,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “If the results found here are applicable to human disease, they tell us that early intervention, before neurodegeneration begins, may be feasible and therapeutic. These models also provide important tools to develop biomarkers, or disease signatures, which could be invaluable in the design of the clinical trial targeting mutant C9orf72.”

Drs. Baloh and Brown are both hopeful that these mice will be a valuable resource for the ALS research community worldwide and confirm that the models will be shared. The Baloh lab mice will be available through his collaborator, Dr. Cathleen Lutz, at the Jackson Laboratory. The Brown lab mice are available through the University of Massachusetts Medical School.

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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