The ALS Association

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Carrie Martin Munk
The ALS Association
(571) 319-3047



Antisense for the Most Common ALS Gene Corrects Cell Dysfunction

Washington, D.C. (October 18, 2013) — In work supported by The ALS Association, researchers have shown that reducing the product of an ALS-causing gene mutation corrects several key problems caused by the gene. This demonstration provides support for moving this therapy forward in people with ALS whose disease is caused by mutations in this gene, called C9orf72. The study was published in the journal Neuron.

ALS (amyotrophic lateral sclerosis), often referred to 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.

“These findings provide a great deal of support for targeting the C9orf72 gene products directly, in people whose ALS is due to this gene mutation,” said Lucie Bruijn, Ph.D., Chief Scientist for The Association.

The C9orf72 gene is the most common genetic cause of ALS, accounting for more than a quarter of all familial cases and more than 5 percent of sporadic cases. The mutation is a large expansion of a six-nucleotide repeat unit, GGGGCC. The normal gene contains no more than 30 of these units, while the mutant gene may contain many dozens to hundreds of them. The mutant gene produces a long and sticky strand of RNA, which clumps together, interfering with cell function through unknown means.

In the current study, the authors used so-called antisense oligonucleotides (ASOs) to trigger degradation of the RNA aggregates. Treatment with ASOs reduced the RNA aggregates, corrected a mutation-induced pattern of aberrant gene expression, and reduced the cell’s susceptibility to overexcitation and death. The work was performed in skin cells taken from individuals with ALS and transformed into motor neurons, the cells whose death causesthe disease.

The research was performed by Christopher Donnelly, Ph.D., and colleagues under the direction of Rita Sattler, Ph.D., and Jeffrey Rothstein, M.D., Ph.D., all of Johns Hopkins University in Baltimore, Md., supported through a milestone-driven drug discovery contract as part of TREAT ALS™. ISIS Pharmaceuticals is working in partnership with this study to provide the ASO’s. Academic-industry partnerships are critical to help move therapies into the clinic.

Funding for this study was made possible through The Neil Brourman, M.D. ALS Research Fund. ALS Association chapters also provide ongoing and generous support to fund The Association’s research grants. Chapters continually work with certified centers and clinics to provide the best care to people living with ALS.

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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