Understanding NK cells in ALS

Natural killer (NK) cells are a type of immune cell that helps the body fight infections and clear out abnormal cells.  However, researchers have shown that in amyotrophic lateral sclerosis (ALS) dysregulated NK cells are capable of damaging motor neurons, associating them with ALS progression.  However, exactly how this happens remains unclear.

Researchers led by Stephen Goutman, M.D., M.S., Harriet Hiller Research Professor, and Benjamin Murdock, Ph.D., Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar, examined NK cell gene expression in ALS patients. Their goal was to discover specific dysregulated genes and pathways over the course of the disease in an effort to identify potential new therapy targets. Their results were recently published in Neurology Open Access.

“We compared blood samples from people with ALS at early and later timepoints with healthy controls,” explained Dr. Murdock.  “We found widespread disruptions in immune-related genes, including reduced activity from the body’s usual immune response early in the disease and increased activity of different immune-related genes later in the disease.”

“These findings are important because they suggest that NK cells become increasingly altered as ALS progresses,” said Dr. Goutman.  “Targeting specific NK cell pathways may offer a promising new therapeutic strategy, and further work is needed to identify and understand the timing of such therapies.”

Other authors: Kai Guo, Ph.D., Jihyun Park, Ph.D., Dae-Gyu Jang, Ph.D., Samuel Teener, Ian Webber-Davis, Joshua Famie, and Caroline Piecuch, from the University of Michigan, and Junguk Hur, Ph.D., from University of North Dakota.

Support for this research includes the National Institutes of Health, National Institute of Neurological Disorders and Stroke, Department of Defense, ALS Association, Rober A. Epstein and Joan Chernoff-Epstein Emerging Scholar Fund, Dr. Randal Whitcomb Fund for ALS Genetics, Coleman Therapeutic Discovery Fund, Peter R. Clark Fund for ALS Research, James and Margaret Hiller, and Eric and Linda Novak.

Paper cited: Goutman SA, Guo K, Park J, Jang DG, Teener SJ, Webber-Davis IF, Famie JP, Piecuch CE, Hur J, Murdock BJ. Natural Killer Cell Dysregulation During ALS Disease Progression: A Gene Expression Analysis. Neurol Open Access. 2026 Mar;2(1):e000067. doi: 10.1212/wn9.0000000000000067. Epub 2026 Feb 9. PMID: 41684905; PMCID: PMC12893619.