Therapeutic Potential of Targeting SARM1 in ALS: Anna Underhill, BS


The postdoctoral researcher at King’s College London discussed the mechanistic role SARM1 gene mutations play in the development and progression of ALS. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

“We know that knocking out Sarm1 in mouse models protects the neurons, and SARM1 could potentially be targeted for treating ALS. SARM1 is really interesting because of its role downstream in the pathway for Wallerian degeneration.”

Many diseases, including amyotrophic lateral sclerosis (ALS), are linked to errors, or mutations, in genes. About two-thirds of individuals with familial ALS and 10% of people with sporadic or singleton ALS have a known ALS-associated genetic mutation. There are several well-known ALS genes, including C9orf72, SOD1, NEK1, TDP43, and fused in sarcoma (FUS). Another gene, SARM1, and the protein it produces, have shown to cause death of nerve fibers and their supporting neurons.

Researchers have also found that SARM1 mutations thought to promote neuron death are present in ALS. The ALS Association, in collaboration with ALS Finding a Cure, recently awarded $400,000 to support research into the role SARM1 gene mutations play in the development and progression of ALS. Led by Jemeen Sreedharan, PhD, MBBS, MRCP, of King’s College London and Michael Coleman, PhD, of Cambridge University, the project aims to confirm the proposed role of the novel genetic risk factor, identify other risk factors it interacts with, and explore its wider roles in ALS.

To learn more about the initiative, including the specific potential SARM1 has, NeurologyLive® sat down with study investigator Anna Underhill, BS. Underhill, a postdoctoral researcher at King’s College London, provided context on what had previously been researched, the downstream effects from this gene, and why it holds potential as a therapeutic target.

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