Two years’ effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis

Abstract

Background: Data on the effect of dimethyl fumarate (DMF) on focal and diffuse gray matter (GM) damage, a relevant pathological substrate of multiple sclerosis (MS)-related disability are lacking. Objective: To evaluate the DMF effect on cortical lesions (CLs) accumulation and global and regional GM atrophy in subjects with relapsing–remitting MS. Methods: A total of 148 patients (mean age 38.1 ± 9.7 years) treated with DMF ended a 2-year longitudinal study. All underwent regular Expanded Disability Status Scale (EDSS assessment), and at least two 3T-magnetic resonance imaging (MRI) at 3 and 24 months after DMF initiation. CLs and changes in global and regional atrophy of several brain regions were compared with 47 untreated age and sex-matched patients. Results: DMF-treated patients showed lower CLs accumulation (median 0[0–3] vs 2[0–7], p < 0.001) with respect to controls. Global cortical thickness ( p < 0.001) and regional thickness and volume were lower in treated group (cerebellum, hippocampus, caudate, and putamen: p < 0.001; thalamus p = 0.03). Lower relapse rate (14% vs 40%, p < 0.001), EDSS change (0.2 ± 0.4 vs 0.4 ± 0.9, p < 0.001), and new WM lesions (median 0[0–5] vs 2[0–6], p < 0.001) were reported. No severe adverse drug reactions occurred. Conclusions: Beyond the well-known effect on disease activity, these results provide evidence of the effect of DMF through reduced progression of focal and diffuse GM damage.

Imaging cortical lesions in multiple sclerosis

“…A reduction in cortical lesion accrual rate has been used to assess disease-modifying treatment efficacy in a few longitudinal studies. Compared to placebo, Interferon beta-1a, Glatiramer acetate, and Dimethyl-fumarate were found to prevent the development of new cortical lesions [67,68]. Natalizumab proved a higher efficacy versus Fingolimod [69] when cortical lesions assessment was included in the “no evidence of disease activity” evaluation.…”

Neutrophil Nanovesicle Protects against Experimental Autoimmune Encephalomyelitis through Enhancing Myelin Clearance by Microglia

“…3 Specifically, myelin-specific T cells infiltrate into the central nervous system (CNS) and attack myelin sheath to induce neuronal injury. 4−6 Accordingly, disease-modifying therapies (DMTs) approved by the U.S. Food and Drug Administration (FDA) mainly focus on inhibiting lymphocytes proliferation, including interferon beta (IFN-β), 7 glatiramer acetate (GA), 8 monoclonal antibodies (natalizumab, alemtuzumab, daclizumab and ocrelizumab), 9−11 mitoxantrone, 12 fingolimode, 13 dimethyl fumarates, 14 and teriflunomide. 15 Although these drugs reduce disease recurrence, they do not repair damaged myelin.…”

“…MS patients or experimental models (i.e., experimental autoimmune encephalomyelitis, EAE) are characterized by T cell-mediated demyelination. , The blood–brain barrier (BBB) in MS patients is compromised, resulting in an uncontrolled influx of peripheral immune cells . Specifically, myelin-specific T cells infiltrate into the central nervous system (CNS) and attack myelin sheath to induce neuronal injury. − Accordingly, disease-modifying therapies (DMTs) approved by the U.S. Food and Drug Administration (FDA) mainly focus on inhibiting lymphocytes proliferation, including interferon beta (IFN-β), glatiramer acetate (GA), monoclonal antibodies (natalizumab, alemtuzumab, daclizumab and ocrelizumab), − mitoxantrone, fingolimode, dimethyl fumarates, and teriflunomide . Although these drugs reduce disease recurrence, they do not repair damaged myelin.…”