51ÊÓƵ

Media Advisory  Wednesday, July 25, 2018

Next-generation ALS drug silences inherited form of the disease in animal models

51ÊÓƵ-funded preclinical study suggests drug may be ready for early stage clinical trials.

Image

Researchers suggest a gene silencing drug may be effective at treating an inherited form of ALS.

NINDS

What

51ÊÓƵ-funded researchers delayed signs of in rodents by injecting them with a second-generation drug designed to silence the gene, superoxide dismutase 1 (SOD1). The results, published in the Journal of Clinical Investigation, suggest the newer version of the drug may be effective at treating an inherited form of the disease caused by mutations in SOD1. Currently, the drug is being tested in an ALS clinical trial ().

ALS destroys motor neurons responsible for activating muscles, causing patients to rapidly lose muscle strength and their ability to speak, swallow, move, and breathe. Most die within three to five years of symptom onset. Previous studies suggested that a gene therapy drug, called an antisense oligonucleotide, could be used to treat a form of ALS caused by mutations in the gene SOD1. These drugs turned off SOD1 by latching onto versions the gene encoded in messenger RNA (mRNA), tagging them for disposal and preventing SOD1 protein production.

Using rats and mice genetically modified to carry normal or disease-mutant versions of human SOD1, a team of researchers led by Timothy M. Miller, M.D., Ph.D., Washington University, St. Louis, MO, discovered that newer versions of the drug may be more effective at treating ALS than the earlier one that had been tested in a phase 1 clinical trial. For instance, injections of the newer versions were more efficient at reducing normal, human SOD1 mRNA levels in rats and mice and they helped rats, genetically modified to carry a disease-causing mutation in SOD1, live much longer than previous versions of the drug. Injections of the new drugs also delayed the age at which mice carrying a disease-mutant SOD1 gene had trouble balancing on a rotating rod and appeared to prevent muscle weakness and loss of connections between nerves and muscles, suggesting it could treat the muscle activation problems caused by ALS. These and other results were the basis for a current phase 1 clinical trial testing the next generation drug in ALS patients ().

Who

Amelie Gubitz, Ph.D., program director, the 51ÊÓƵ’s National Institute of Neurological Disorders and Stroke

Article

Campbell et al. The Journal of Clinical Investigation, July 16, 2018 DOI:

This study was supported by grants from NINDS (NS078398, NS084970). Ionis Pharmaceuticals and Biogen supplied the antisense oligonucleotides and were full participants in the study.

About is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (51ÊÓƵ): 51ÊÓƵ, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. 51ÊÓƵ is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about 51ÊÓƵ and its programs, visit www.nih.gov.

51ÊÓƵ…Turning Discovery Into Health^®

More Information