A new study offers clues as to why exercise can improve neurological symptoms in people with multiple sclerosis (MS). The study, led by investigators from Mass General Brigham and University Medical Center Hamburg-Eppendorf (UKE), examined levels of the exercise hormone irisin in a mouse model of multiple sclerosis. Researchers found that irisin reduced both clinical symptoms and the loss of neurons in the experimental model. Additionally, when irisin was removed, the protective effects of exercise disappeared. Taken together, the researchers’ findings suggest that irisin can protect neurons from inflammation-driven neurodegeneration, offering a potential target for future MS therapies. Results are published in Nature Metabolism .
“We are optimistic that our study will open up further developments of irisin as a therapeutic for, in particular, progressive MS,” said senior and corresponding author Christiane D. Wrann, DVM, PhD , a neuroscientist and leader of the Program in Neuroprotection in Exercise at Mass General Brigham Neuroscience Institute and the McCance Center for Brain Health at Massachusetts General Hospital. “Our findings strengthen the argument that irisin can help protect neurons in the context of multiple types of neurodegenerative diseases.”
MS is a chronic, autoimmune-mediated neurodegenerative disease in which the immune system attacks the myelin sheaths that swath neurons in the brain and spinal cord. Current therapies for MS reduce inflammation but do not adequately prevent neurodegeneration. Research from other groups has shown that aerobic exercise can improve MS symptoms, but the exact mechanisms have been unknown.
Wrann and colleagues have previously shown that the hormone irisin, produced by muscles during exercise, can improve cognitive function and neuroinflammation in mouse models of Alzheimer’s disease . In their new federally funded study of MS, researchers also found evidence of neuroprotective effects. In the MS model, deleting irisin canceled out the protective effects of exercise while adding irisin back rescued neurons and improved disease outcomes. Irisin reduced neuronal loss in three central nervous system compartments: spinal cord, hippocampus, and retina, reduced loss of synapses and restored a neuroprotective gene program.
"What we find particularly exciting is that an exercise-induced molecule can directly protect neurons in a mouse model of multiple sclerosis, revealing a fundamentally new mechanism by which exercise can influence neurodegeneration in MS,” said Sina C. Rosenkranz, MD, first author and head of the Behavioral Interventions group at the Institute for Neuroimmunology and Multiple Sclerosis (INIMS) at UKE. Rosenkranz is a former postdoctoral fellow in the Wrann lab.
“Interestingly, in the current study we did not find a direct suppressive effect of irisin on peripheral immunity, but rather direct neuroprotective effects,” said Ruxandra F. Sîrbulescu, PhD, co-senior author on the study, a neuroimmunologist at Mass General Brigham Neuroscience Institute and leader of the Regenerative Medicine program at the Vaccine and Immunotherapy Center .
The authors note that more research is needed to understand how irisin’s protective mechanism works. They also note that it’s important to remember that the benefits of exercise in multiple sclerosis are complex and likely involve multiple factors, not just irisin alone. The team plans to continue investigating the hormone’s effects and mechanisms in future studies.
Authorship: In addition to Wrann, Rosenkranz, and Sîrbulescu, co-authors include Joana F. da Rocha, Luis Moreira, Pius Schlachter, Jasmina Bier, Kaela Healy, Daniela Neves Silva, Mohamed Ariff Iqbal, Marjan Gharagozloo, Yueyue Xiong, Matthew A. Murphy, Helena C. Lichtenfeld, Lukas Raich, Michaela Schweizer, Asude Ertaş, Marcel S. Woo, Vanessa Vieira, Samuel E. Honeycutt, James P. White, Gregory A. Wyant, Manuel A. Friese, and Peter A. Calabresi.
Disclosures: Wrann holds a patent related to irisin (WO2015051007A1). Wrann is an academic co-founder and consultant for Aevum Therapeutics. Wrann has a financial interest in Aevum Therapeutics, a company developing drugs which harness the protective molecular mechanisms of exercise to treat neurodegenerative and neuromuscular disorders. Wrann received honoraria from Novartis outside the scope of this work. Wrann’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. Rosenkranz has received speaker honoraria from Merck, Roche and Sanofi, all outside of this work. Calabresi has received consulting fees from Lilly and Novartis and is PI on a grant to JHU from Genentech. Woo received honoraria from Lilly and Eisai outside the scope of this work.
Funding: This work was supported in part by the National Institutes of Health (NS117694, AG062904, AG064580, AG072054, NS117598, NS041435, R56AG056664, T32AG07057); the Cure Alzheimer’s Fund; a SPARC Award from the McCance Center for Brain Health; the Hassenfeld Clinical Scholar Award; the Claflin Distinguished Scholar Award; the Boehringer Ingelheim Fonds travel grant; the Advanced Clinician–Scientist Fellowship from the Federal Ministry of Education and Research, Germany (iSTAR 01EO2106); the Gemeinnützige Hertie‑Stiftung (P1200012, P1250014); the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—project 523862973); a National MS Society Career Transition Grant (TA‑2104‑37423); and the Else‑Kröner‑Fresenius‑Foundation.
Paper cited: Rosenkranz SC et al. “The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis” Nature Metabolism DOI: 10.1038/s42255-026-01527-7
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Nature Metabolism
Observational study
Animals
The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis
21-May-2026
Wrann holds a patent related to irisin (WO2015051007A1). Wrann is an academic co-founder and consultant for Aevum Therapeutics. Wrann has a financial interest in Aevum Therapeutics, a company developing drugs which harness the protective molecular mechanisms of exercise to treat neurodegenerative and neuromuscular disorders. Wrann received honoraria from Novartis outside the scope of this work. Wrann’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. Rosenkranz has received speaker honoraria from Merck, Roche and Sanofi, all outside of this work. Calabresi has received consulting fees from Lilly and Novartis and is PI on a grant to JHU from Genentech. Woo received honoraria from Lilly and Eisai outside the scope of this work.