The ALS Association

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



Unprecedented Details Reported of ALS Gene Mutation’s Effects

Washington, D.C. (March 5, 2014)—In work supported by The ALS Association, researchers have discovered significant new details of the pathological effects of the most common ALS gene. The study was published in the journal Nature.

ALS (amyotrophic lateral sclerosis), otherwise known 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. 

The study, led by Association-supported researcher Jiou Wang, Ph.D., of Johns Hopkins University in Baltimore, Md., focused on the C9ORF72 gene, mutations in which account for up to 40 percent of familial ALS and 6 percent of sporadic ALS. The mutation is an expansion of a six-nucleotide GGGGCC section of the gene (a hexanucleotide repeat expansion, or HRE). The normal gene contains as few as two of these GGGGCC units; the mutated gene may contain hundreds to thousands. Nucleotides are the building blocks for both DNA, which makes up genes, and RNA, which carries genetic messages used to make proteins.

The researchers found that the expanded section of the gene folded into unusual looped structures, like spaghetti sticking to itself. These structures (called G-quadruplexes) formed in both the expanded DNA of the gene and the expanded RNA. The structures reduced the amount of protein that could be made from the gene and trapped multiple cell proteins that are involved in controlling gene expression. Cells from people with ALS due to C9ORF72 displayed changes under the microscope, suggesting these structures caused stress in the cell nucleus, potentially contributing to disease. This study was funded by Mrs. Corinne Schwartz and Family.

“This important study gives us an unprecedented look at the effects of the C9ORF72 mutation,” said Lucie Bruijn, Ph.D., MBA, Chief Scientist for The Association. “It is now imperative that we follow up these observations with further work to clarify how these changes affect disease onset or progression. These insights will be critical in designing therapies to interrupt these processes.”

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