Repurposed ALS drug shows promise in mouse model of rare childhood genetic disorder – National Institutes of Health

Media Advisory

Friday, November 19, 2021

NPC1 leads to difficulty controlling movements, liver and lung disease, impaired swallowing, intellectual decline and death.

Riluzole, a drug approved to treat amyotrophic lateral sclerosis (ALS), a disease affecting nerve cells controlling movement, could slow the gradual loss of a particular brain cell that occurs in Niemann-Pick disease type C1 (NPC1), a rare genetic disorder affecting children and adolescents, suggests a study in mice by scientists at the National Institutes of Health.

The study was conducted by Forbes D. Porter, M.D., Ph.D., of NIHs Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues in the National Human Genome Research Institute and National Institute of Arthritis and Musculoskeletal and Skin Disease. It appears in Molecular Genetics and Metabolism. The study was supported in part by a grant from the Ara Parseghian Medical Research Foundation.

NPC1 results from an impaired ability to move cholesterol through cells, leading to difficulty controlling movements, liver and lung disease, impaired swallowing, intellectual decline and death. Much of the movement difficulties in NPC1 result from gradual loss of brain cells known as Purkinje neurons. The researchers found that mice with a form of NPC1 have a diminished ability to lower levels of glutamate a brain chemical that stimulates neurons after it has bound to a neurons surface. High levels of glutamate can be toxic to cells. The researchers believe the buildup of glutamate contributes to the brain cell loss seen in the disease. Riluzole blocks the release of glutamate and hence delays the progression of ALS in people.

In the current study, mice with NPC1 survived 12% longer when treated with riluzole, compared to untreated mice. The researchers believe that riluzole or similar drugs may provide a way to slow disease progression in patients with NPC1.

Forbes D. Porter, M.D., Ph.D., NICHD Clinical Director, is available for comment.

Cougnoux, A., et al Reduction of glutamate toxicity: a novel therapeutic approach for Niemann-Pick disease, type C1. Molecular Genetics and Metabolism. 2021.

This media availability describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD leads research and training to understand human development, improve reproductive health, enhance the lives of children and adolescents, and optimize abilities for all. For more information, visit https://www.nichd.nih.gov.

About the National Institutes of Health (NIH):NIH, 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. NIH 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 NIH and its programs, visit http://www.nih.gov.

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Repurposed ALS drug shows promise in mouse model of rare childhood genetic disorder - National Institutes of Health