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Selective Brain Network and Cellular Responses Upon Dimethyl Fumarate Immunomodulation in Multiple Sclerosis
Dumitru Ciolac1,2,3, Felix Luessi1, Gabriel Gonzalez-Escamilla1
1Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Frontiers in Immunology
|August 17, 2019
Summary
Dimethyl fumarate (DMF) treatment in multiple sclerosis (MS) shows varied responses. Patients with greater CD8+ T cell depletion under DMF had better brain network integrity and less atrophy, suggesting personalized treatment potential.
Area of Science:
- Neuroimmunology
- Neuroscience
- Radiology
Background:
- Multiple sclerosis (MS) requires personalized therapies to mitigate gray (GM) and white matter (WM) damage.
- Disease-modifying drugs (DMDs) are effective, but personalized response markers are needed.
- This study investigates brain network and immune cell responses to dimethyl fumarate (DMF) in real-world MS patients.
Purpose of the Study:
- To identify patients with favorable brain network and immune cell dynamics under DMF treatment.
- To compare treatment responses between DMF and natalizumab (NAT) in matched MS cohorts.
- To establish markers for personalized MS therapy.
Main Methods:
- A cohort of 78 MS patients were analyzed over 16 months, comparing DMF (n=42) and NAT (n=36) groups.
- Cortical atrophy and deep GM volumes were quantified; GM and WM network modularization assessed structural changes.
- Lymphocyte subsets in the DMF group were analyzed via flow cytometry and correlated with MRI and clinical data.
Main Results:
- Higher disease activity was observed in the DMF group (60%) compared to NAT (36%).
- DMF treatment showed increased cortical atrophy (-2.4%) versus NAT (-2.1%).
- DMF responders (DMF_R) exhibited significantly lower CD8+ T cell counts (197.7/μl) and less cortical atrophy (-1.7%) compared to non-responders (DMF_NR; 298.4/μl and -3.2%).
Conclusions:
- Natalizumab (NAT) demonstrated a lower rate of cortical atrophy than dimethyl fumarate (DMF).
- DMF-treated patients with substantial CD8+ T cell depletion showed better outcomes in cortical integrity and brain network responses.
- Findings support developing personalized treatment strategies for MS based on immune cell dynamics.
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