One step closer to a blood test for diagnosing ALS

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease with a survival of only two to four years from diagnosis.  ALS remains challenging to identify in routine clinical practice because patients manifest symptoms and signs like those in more common illnesses, and misdiagnoses and errors are frequent.  Because of this, the median time it takes for a definitive ALS diagnosis is five to 15 months and up to 19 months for some patients.  

This delay postpones treatment, which adversely affects survival.  Also, a delayed diagnosis excludes many patients from clinical trials, which usually recruit patients with less advanced disease.  Furthermore, it leaves patients with less time to organize their financial, legal, psychological, and spiritual affairs.  Improved approaches are urgently needed to shorten diagnostic delays for ALS patients.

In research published in Nature Communications, a team led by Eva L. Feldman, M.D., Ph.D., analyzed blood samples from people with ALS and healthy individuals and identified distinct gene expression patterns that distinguish ALS patients.  

“These genetic ‘signatures’ reveal changes in biological pathways involved in disease progression,” explained Dr. Feldman.  “Our finding suggests that, in the future, a simple blood test could help detect ALS earlier and support more personalized approaches to care.”

Next steps require testing the utility of this tool in other ALS settings, including how it would rule out “ALS mimics” and would act in presymptomatic ALS mutation cases.  In the long term, researchers envision being able to translate this research into earlier ALS diagnosis and more accurate anticipated survival times, resulting, most importantly, in more effective treatment for ALS patients.

This study was supported by the National Institute of Neurological Disorders and Stroke, National ALS Registry/CDC/Agency for Toxic Substances and Disease Registry, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences at the National Institutes of Health, Intramural Research Program of the National Institute on Aging, ALS Association, James and Margaret Hiller, Eric and Linda Novak, the Coleman Therapeutic Discovery Fund, the Peter R. Clark Fund for ALS Research, the Sinai Medical Staff Foundation, the Scott L. Pranger ALS Clinic Fund, the Dr. Randall W. Whitcomb Fund for ALS Genetics, the Richard Stravitz Foundation, and the Stanford Morris ALS Research Fund.

Paper cited: Zhao Y, Savelieff MG, Li X, Guo K, Wang K, Li M, Li B, Iyer G, Sakowski SA, Zhao L, Teener SJ, Bakulski KM, Dou JF, Traynor BJ, Karnovsky A, Batterman SA, Hur J, Goutman SA, Sartor MA, Feldman EL. Gene expression signatures from whole blood predict amyotrophic lateral sclerosis case status and survival. Nat Commun. 2025 Oct 31;16(1):9631. doi: 10.1038/s41467-025-64622-5. PMID: 41173979; PMCID: PMC12579231.