The ALS Association

ALS Ice Bucket Challenge Progress

New ALS Therapy Target Highlights Role of RNA Processing in the Disease

June 18, 2015

Researchers have identified a new therapy development target that strengthens the evidence that defects in cellular processing of RNA are important in the development of ALS. The identification of this new target may be relevant to over 90 percent of people with ALS.

The research showed that motor neurons can be protected from disease-related toxicity by human up-frameshift protein 1 (hUPF1). When either of two disease-related proteins, called FUS and TDP43, were expressed in cultures of motor neurons at levels sufficient to cause neuronal death, co-expression of hUPF1 saved up to half the neurons.

The researchers, including The ALS Association-supported scientist Steven Finkbeiner, M.D., Ph.D., of the Gladstone Institutes in San Francisco, showed that the protective effect was due to its promotion of a process called nonsense-mediated decay of messenger RNA (mRNA). mRNA is an essential cellular messenger between genes and the proteins they encode. Disturbance of mRNA processing has been implicated in several forms of ALS. hUPF1 did not protect against ALS due to mutations in the SOD1 gene, which is not believed to involve disruption of mRNA processing.

“These important results tell us in even stronger terms that ALS is not a single disease,” according to Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “These findings emphasize the importance of RNA processing for most forms of ALS, and suggest that promoting hUPF1 might be therapeutic. They also tell us that therapies for SOD1-related ALS might require different strategies and that clinical trials may have the greatest chance of success if they target people with similar forms of ALS.”

Read the Press Release.

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