How ALS affects neutrophils

The immune system has been consistently implicated in driving amyotrophic lateral sclerosis (ALS).  One particular population of immune cells, neutrophils, likely play a critical role in disease. Higher neutrophil levels are associated with shorter survival, and neutrophil levels can be used predict ALS progression.  However, it is unclear exactly how neutrophils impact ALS.

To investigate this question, research is being led by Benjamin Murdock, Ph.D., the Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar. He and his team are examining neutrophil biomarkers in the blood of ALS patients to identify which neutrophil mechanisms may contribute to the disease. These biomarkers include calprotectin for general activation, MMP9 for trafficking, NGAL for degranulation, and double-stranded DNA for the formation of neutrophil extracellular traps (NETs).

They found that all of these biomarkers were upregulated in ALS, suggesting that neutrophils are generally more highly activated in the disease.  However, only NET formation was associated with shorter survival, and only in female patients.  This implies that therapies targeting NET formation may be beneficial to women with ALS.

“This is another step towards personalized medicine in ALS, which is how we believe it needs to be treated,” explained Dr. Murdock.  “We are learning that not all ALS patients have the same underlying mechanisms driving the disease.  Future studies will need to identify and address multiple disease mechanisms, identifying potential therapy targets for ALS.”

Other authors: Lillia Baird, Ph.D., Haley McQuown, Jihyun Park, Ph.D., Samuel Teener, Ian Webber-Davis, Andrew Carter, Dae-Gyu Jang, Ph.D., Eva L. Feldman, M.D., Ph.D., and Stephen Goutman, M.D., M.S., all from the University of Michigan.

Funding for this research is provided by the National Institutes of Health, Centers for Disease Control and Prevention, Richard Stravitz Foundation, Peter R. Clark Fund for ALS Research, Coleman Therapeutic Discovery Fund, Standford Morris ALS Research Fund, Michael R. Johns Fund, and Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund.

Paper cited: Baird LA, McQuown H, Park J, Teener SJ, Webber-Davis IF, Carter AD, Jang DG, Feldman EL, Goutman SA, Murdock BJ. Peripheral Neutrophil Activation and Extracellular Trap Formation in Amyotrophic Lateral Sclerosis. Ann Clin Transl Neurol. 2026 May 14. doi: 10.1002/acn3.70431. Epub ahead of print. PMID: 42135919.