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

•Exercise therapy might induce disease-modifying effects in multiple sclerosis•BDNF, NfL and GFAP may reflect neurogenesis, axonal damage and astrocyte reactivity•Serum BDNF, NfL and GFAP did not change due to high intensity aerobic training Neuroinflammation and neurodegeneration are pathological h...

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Published in:	Multiple sclerosis and related disorders 2023-02, Vol.70, p.104489-104489, Article 104489
Main Authors:	Gravesteijn, Arianne S, Beckerman, Heleen, Willemse, Eline AJ, Hulst, Hanneke E, de Jong, Brigit A, Teunissen, Charlotte E, de Groot, Vincent
Format:	Article
Language:	eng
Subjects:	Biomarkers Brain-Derived Neurotrophic Factor Exercise Female Glial Fibrillary Acidic Protein Humans Intermediate Filaments - pathology Male Middle Aged Multiple sclerosis Multiple Sclerosis - pathology Neurofilament proteins Neuroprotection Neuroprotective Agents
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Summary:	•Exercise therapy might induce disease-modifying effects in multiple sclerosis•BDNF, NfL and GFAP may reflect neurogenesis, axonal damage and astrocyte reactivity•Serum BDNF, NfL and GFAP did not change due to high intensity aerobic training 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 hypothesize that exercise has a neuroprotective effect on MS reflected by normalization of BDNF, NfL and GFAP levels. 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). 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 technology. 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. 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 (β = 0.11, 95%CI (-3.78 to 4.00)), NfL (β = -0.04, 95%CI (-0.26 to 0.18)), and GFAP (β = -0.01, 95%CI (-0.16 to 0.15)), adjusted for confounders. Aerobic exercise therapy did not result in statistically significant changes in the tested neuro-specific blood-based biomarkers in people with MS. this study is registered under number ISRCTN69520623 (https://www.isrctn.com/ISRCTN695206).
ISSN:	2211-0348 2211-0356