FOR IMMEDIATE RELEASE

Discovery Funded By The ALS Association Points to Common Pathways for Two ALS Genes

Washington, D.C. (October 4, 2012)—Researchers supported by The ALS Association have discovered close links between the two genes that cause ALS, FUS and TDP-43, according to research published in the September 30 online edition of Nature Neuroscience. The discovery improves knowledge of how each gene is likely to cause disease and focuses attention on the common pathways they share as likely targets for the development of potential therapies.

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.

“This discovery shows us several important features of these two genes,” according to ALS Association Chief Scientist Lucie Bruijn, Ph.D. “Using these insights will help direct us to the most promising routes for developing treatments against ALS.”

The study was led by Clotilde Lagier-Tourenne, Ph.D.; Magdalini Polymenidou, Ph.D.; and Kasey Hutt, Ph.D., working with Principal Investigator Don Cleveland, Ph.D., all from the Department of Cellular and Molecular Medicine at the University of California at San Diego.

Dr. Lagier-Tourenne is a recipient of the The ALS Association’s Milton Safenowitz Post-Doctoral Fellowship for ALS Research, which provides young post-doctoral students with the unique opportunity to stand at the forefront of ALS research and partner with the best scientific minds in the quest for a cure. The fellowship is made possible through a grant from Marilyn Safenowitz and the Milton and Marilyn Safenowitz Family Foundation through The ALS Association’s Greater New York Chapter. It is named in memory of Milton Safenowitz, who died from ALS in 1998.

The study examined the detailed workings of the protein made from the FUS gene, a known cause of ALS. The normal function of the FUS protein is to bind to RNA, the cellular “messenger” that carries genetic instructions from the cell nucleus, where they are stored, to the cell cytoplasm, where they are used to make proteins.

The researchers found that the FUS protein preferentially bound to RNA from genes with especially long “introns,” or non-coding genetic sequences, possibly to make sure these genes are properly decoded. Loss of FUS protein led to reduced levels of several proteins important for neuron development and function. This suggests that the FUS mutations that cause ALS do so through loss of the normal FUS protein function in the neuron.

The researchers also found that the protein from another ALS-causing gene, TDP-43, also bound to some of the same genes as FUS, suggesting these may be especially crucial for normal neuron function. That possibility was strengthened by the finding that the proteins made from these genes were deficient in motor neurons from ALS patients. Restoring the normal decoding of these genes, or compensating for their absence, may be a valuable therapeutic strategy.

“Understanding how mutations in FUS and TDP-43 contribute to ALS is crucial,” Dr. Bruijn said, “and this study points toward something important they have in common that may be crucial for the disease. We are encouraged by this finding, as it can help us determine how to develop treatments to overcome the losses caused by these mutations.”

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 www.alsa.org.