Project Grant R01NS151040

The National Institute of Neurological Disorders and Stroke awarded the University of Massachusetts Medical School $542,777 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to discover and functionally analyze somatic mutations contributing to sporadic amyotrophic lateral sclerosis.

The research combines clinical expertise in ALS genetics with expertise in somatic mutations and single-cell analysis to investigate whether somatic mutations in ALS risk genes can contribute to sporadic ALS development. The work analyzes somatic mutations in spinal cord tissue from 151 ALS cases and controls banked by the Brown Laboratory, in a consortium-generated whole-genome sequencing dataset comprising more than 500 cases, and in monozygotic twins discordant for ALS onset. Predicted deleterious mutations will be functionally validated using single-cell multiomics and in vitro modeling of CRISPR-edited human iPSC-derived motor-neuron-like cells, with experiments designed to identify somatic mutations affecting sporadic ALS at all embryonic stages, including early somatic mutations distributed throughout the body and late embryonic somatic mutations restricted to the brain and spinal cord.

The award period runs from September 1, 2026, through August 31, 2031. Work is performed at the University of Massachusetts Medical School in Worcester, Massachusetts. This is a project grant.