The ALS Association

ALS Ice Bucket Challenge Progress
Carrie Munk
The ALS Association
(571) 319-3047



New Study Points to Protein, not RNA, as Culprit in C9orf72 ALS

Washington, D.C. (September 24, 2015) — Abnormal protein production, not RNA aggregation, damages neurons in the most common genetic form of ALS, according to new ALS Association-funded research. The study was published in the journal Neuron.

ALS (amyotrophic lateral sclerosis) 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.

Mutation in the C9orf72 gene is the most common genetic cause of ALS, accounting for up to 40% of all familial disease and six percent of sporadic disease. The mutation is an expansion of a six-nucleotide repeat, GGGGCC, from as few as two units in the normal gene to hundreds or even thousands in the mutated form. Production of RNA from the mutation leads to two potentially harmful consequences: accumulation of this RNA in the cell nucleus and production of unusual “dipeptide repeat” proteins. Researchers are actively investigating which of these two consequences may contribute to neuron death in ALS.

In the new study, Helene Tran, Ph.D., and Fen-Biao Gao, Ph.D., both of the University of Massachusetts Medical School in Worcester, and colleagues, showed that abundant accumulation of RNA in the nucleus did not affect neuronal survival. In contrast, damage to neurons from dipeptide repeat proteins was significant, and a temperature-related increase in toxicity was proportional to the increased production of the proteins, not the accumulation of RNA. Based on their results, they suggest that treatments aimed at reducing the effects of the proteins might be therapeutic.

The research was performed in fruit flies, which were also used in several other recent studies investigating the pathogenic mechanism of the C9orf72 mutation. Those studies showed that the mutation impaired transport out of the nucleus; one of the studies demonstrated that the expanded RNA contributed directly to the disease.

“This important paper adds to the growing understanding of the pathogenesis of the C9orf72 gene,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “It will be important to understand whether the differences in mechanism suggested by this group of new studies are due to differences in the models used in each or are pointing toward multiple toxic effects at work at the same time in the disease. As we learn more about the consequences of the gene mutation, we will be able to better target our efforts toward the most effective avenues for reversing those consequences.”

Dr. Tran is a 2012 recipient of the Milton Safenowitz Post-Doctoral Research Fellow Award from The ALS Association, funded through the generosity of the Safenowitz family through the Greater New York Chapter and are in memory of Mr. Safenowitz, who died of ALS in 1998. “It is extremely encouraging as a young scientist to feel supported by The ALS Association,” Dr. Tran said.

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

Powered by Blackbaud
nonprofit software