Exercise Training and Biomarkers of Neuroaxonal Injury in Multiple Sclerosis: Narrative Review

There is increasing interest in exercise training (ET) as a behavior with potential disease-modifying properties in people with multiple sclerosis (MS), as ET has beneficial effects on relapses, lesions, disability, and cognitive-processing speed (CPS) as markers of MS disease progression. There is limited evidence for ET as a behavior that may have disease-modifying properties based on its association with body fluid biomarkers of neuroaxonal injury in MS. This paper involved a narrative review for building a rationale that supports focusing on ET and body fluid biomarkers of neuroaxonal injury in MS, namely, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). We searched the PubMed, EBSCOhost (Medline Ultimate), and EMBASE databases from inception through February 2026 for articles aligning with the focus of this narrative review. The articles indicated that sNfL and sGFAP levels were notably higher in MS than in controls; differed across demographic and clinical variables; and responded beneficially with disease-modifying therapy usage in MS. We further located two meta-analyses examining ET effects on sNfL and sGFAP in MS, and there were significant positive effects on sNfL, but not sGFAP. Researchers should adopt discovery models and experimental medicine frameworks for guiding future randomized controlled trials of ET and biomarkers of neuroaxonal injury in MS.