Abstract
Background:
Oxidative stress is implicated in the pathophysiology of multiple sclerosis (MS), but the potential of oxidative stress responses as biomarkers of MS disease activity and therapeutic response to disease modifying therapy (DMT) has not been systematically explored.
Methods:
To examine peripheral blood oxidative stress profiles in people with MS (pwMS), plasma concentrations and peripheral blood mononuclear cell (PBMC) expression of master antioxidant regulators nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), downstream antioxidant enzymes (superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1), & catalase activity), and plasma end products of oxidation (4-hydroxynonenal (4-HNE), 8-hydroxy-2- deoxyguanosine (8-OHdG), & protein carbonyls) were sampled serially over 12 months, including in a cohort commencing DMT. Multivariable regression models were employed adjusting for age, sex, disease duration, smoking, and repeated measures.
Results:
78 participants (53 relapsing-remitting MS (RRMS), 11 primary progressive MS (PPMS) & 14 secondary progressive MS (SPMS)); and 40 control subjects were included; 12 commenced dimethyl fumarate (DMF), 12 ocrelizumab and 7 natalizumab. Oxidative stress responses varied within and between individuals but dysregulated oxidative stress responses were observed in MS, particularly SPMS. DMT initiation was associated with altered antioxidant responses.
Conclusions:
The data support a role for dysregulated oxidative stress responses in MS. Given the variability observed, the utility of individual oxidative stress components as biomarkers for disease stratification and monitoring is limited. However, additional investigation, including use of a constellation of biomarkers, may have clinical utility and inform regarding MS pathophysiology and therapy.
Oxidative stress is implicated in the pathophysiology of multiple sclerosis (MS), but the potential of oxidative stress responses as biomarkers of MS disease activity and therapeutic response to disease modifying therapy (DMT) has not been systematically explored.
Methods:
To examine peripheral blood oxidative stress profiles in people with MS (pwMS), plasma concentrations and peripheral blood mononuclear cell (PBMC) expression of master antioxidant regulators nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), downstream antioxidant enzymes (superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1), & catalase activity), and plasma end products of oxidation (4-hydroxynonenal (4-HNE), 8-hydroxy-2- deoxyguanosine (8-OHdG), & protein carbonyls) were sampled serially over 12 months, including in a cohort commencing DMT. Multivariable regression models were employed adjusting for age, sex, disease duration, smoking, and repeated measures.
Results:
78 participants (53 relapsing-remitting MS (RRMS), 11 primary progressive MS (PPMS) & 14 secondary progressive MS (SPMS)); and 40 control subjects were included; 12 commenced dimethyl fumarate (DMF), 12 ocrelizumab and 7 natalizumab. Oxidative stress responses varied within and between individuals but dysregulated oxidative stress responses were observed in MS, particularly SPMS. DMT initiation was associated with altered antioxidant responses.
Conclusions:
The data support a role for dysregulated oxidative stress responses in MS. Given the variability observed, the utility of individual oxidative stress components as biomarkers for disease stratification and monitoring is limited. However, additional investigation, including use of a constellation of biomarkers, may have clinical utility and inform regarding MS pathophysiology and therapy.
| Original language | English |
|---|---|
| Journal | Multiple Sclerosis and Related Disorders |
| Publication status | Accepted/In press - 29 Jan 2026 |