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

## TL;DR

This review explores how exercise training might affect biomarkers of nerve damage in multiple sclerosis, potentially helping to develop better treatment strategies.

## Contribution

The paper provides a narrative review linking exercise training to changes in neuroaxonal injury biomarkers in MS, offering a rationale for future clinical trials.

## Key findings

- sNfL and sGFAP levels are higher in MS patients compared to controls.
- Exercise training shows significant positive effects on sNfL levels but not sGFAP.
- Discovery and experimental medicine models are recommended to guide future RCTs on exercise and MS biomarkers.

## Abstract

Public health relevance—how does this work relate to a public health issue?
This review examines how exercise training may influence sNfL and sGFAP levels, as key biomarkers of disease activity and neurodegeneration in MS.

This review examines how exercise training may influence sNfL and sGFAP levels, as key biomarkers of disease activity and neurodegeneration in MS.

Public health significance—why is this work of significance to public health?
Understanding how biomarker levels may be altered by exercise training could advance the identification and understanding of mechanistic pathways driving disability and inform more targeted approaches for interventions.

Understanding how biomarker levels may be altered by exercise training could advance the identification and understanding of mechanistic pathways driving disability and inform more targeted approaches for interventions.

Public health implications—what are the key implications or messages for practitioners, policy makers and/or researchers in public health?
The findings could guide the design of future RCTs concerning sNfL and sGFAP as accessible, cost-effective, and measurable indicators of the neuroprotective effects of exercise training.Implementation of the discovery and experimental medicine models offers a way to strengthen RCT design and supports evidence-based exercise recommendations in MS.

The findings could guide the design of future RCTs concerning sNfL and sGFAP as accessible, cost-effective, and measurable indicators of the neuroprotective effects of exercise training.

Implementation of the discovery and experimental medicine models offers a way to strengthen RCT design and supports evidence-based exercise recommendations in MS.

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.