Brain-derived neurotrophic factor, neurofilament light and glial fibrillary acidic protein do not change in response to aerobic training in people with MS-related fatigue - a secondary analysis of a randomized controlled trial

Background: Neuroinflammation and neurodegeneration are pathological hallmarks of multiple sclerosis (MS). Brain-derived neurotrophic factor (BDNF), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are blood-based biomarkers for neurogenesis, axonal damage and astrocyte reactivity, respectively. We hy-pothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels.Objectives: To investigate the neuroprotective effect of aerobic training (AT) compared to a control intervention on blood-based biomarkers (i.e. BDNF, NfL, GFAP) in people with MS (pwMS). Methods: In the TREFAMS-AT (Treating Fatigue in Multiple Sclerosis -Aerobic Training) study, 89 pwMS were randomly allocated to either a 16-week AT intervention or a control intervention (3 visits to a MS nurse). In this secondary analysis, blood-based biomarker concentrations were measured in 55 patients using Simoa technol-ogy. Changes in pre-and post-intervention concentrations were compared and between-group differences were assessed using analysis of covariance (ANCOVA). Confounding effects of age, sex, MS-related disability assessed using the Expanded Disability Status Scale (EDSS), MS duration, use of disease-modifying medication, and Body Mass Index were considered.Results: Blood samples were available for 30 AT and 25 control group participants (mean age 45.6 years, 71% female, median disease duration 8 years, median EDSS score 2.5). Within-group changes in both study groups were small and non-significant, with the exception of BDNF in the control group (median (interquartile range)-2.1 (-4.7; 0)). No between-group differences were found for any biomarker: BDNF (13 = 0.11, 95%CI (-3.78 to 4.00)), NfL (13 =-0.04, 95%CI (-0.26 to 0.18)), and GFAP (13 =-0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders.Conclusion: Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS.

Automated summary

In the TREFAMS-AT study, it was found that aerobic exercise therapy did not result in significant changes in neuro-specific blood-based biomarkers (BDNF, NfL, and GFAP) in people with MS.