The ALS Association

Ice Bucket Challenge Progress
Carrie Munk
The ALS Association



New C9orf72 Disease Pathway Revealed

Washington, D.C. (October 26, 2016) — Unusual proteins products made by the C9orf72 gene, the most common genetic cause of ALS, disrupt assembly of critical parts of the cell’s protein-making machinery, according to a new study in the journal Cell. The study led by co-authors Kyung-Ha Lee, Ph.D., and Peipei Zhang, Ph.D., along with senior author J. Paul Taylor, M.D., Ph.D., all of St. Jude Children’s Research Hospital in Memphis, Tenn., was supported 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 leads to total paralysis and death, usually 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.

Mutation of the C9orf72 gene leads to production of “dipeptide repeat proteins” (DPRs), which previous studies have suggested may be toxic to motor neurons. In the new study, investigators examined the subcellular distribution and effects of each of the five kinds of DPRs made by the C9orf72 mutation.

The authors found that those DPRs containing the amino acid arginine interacted with multiple RNA binding proteins, which are critical for processing and translating the genetic instructions of all genes. They showed that arginine-containing DPRs altered the assembly, physical properties and function of several types of RNA-related structures, including components of the nucleolus (responsible for manufacturing ribosomes, which build proteins) and stress granules (which serve as temporary storage sites for RNA when cells are under stress).

“This important study advances our understanding of the pathogenesis of ALS due to the C9orf72 mutation,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “This will help us develop therapies to prevent or mitigate the effects of interference with RNA processing demonstrated here. The research also suggests there may be common mechanisms at work in other forms of ALS as well, making these results even more important for understanding the disease as a whole.”

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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