Immunomodulatory Therapies in Multiple Sclerosis Management

Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system characterised by inflammatory demyelination and neurodegeneration. Immunomodulatory therapies aim to recalibrate aberrant immune responses, reducing relapse frequency and slowing disability accumulation while preserving general immune competence. First-line agents such as interferon-β and glatiramer acetate modulate cytokine networks and antigen presentation, whereas small-molecule drugs like dimethyl fumarate activate antioxidant pathways to protect myelin. Sphingosine-1-phosphate receptor modulators restrict lymphocyte egress from lymphoid organs, and monoclonal antibodies (for example natalizumab and alemtuzumab) deplete or block trafficking of pathogenic lymphocyte subsets. Pulsed immune reconstitution therapies such as cladribine and alemtuzumab induce transient lymphodepletion followed by selective renewal of a regulatory immune repertoire. Emerging cell-based approaches deploy tolerogenic dendritic cells to promote antigen-specific tolerance without global immunosuppression. Together, these strategies reflect a shift towards personalised regimens guided by biomarker-driven predictions of efficacy and safety, with the ultimate goal of achieving long-term remission and neuroprotection.

Research from Nature Portfolio

Studies have illuminated mechanisms by which dimethyl fumarate (DMF) exerts its effects on innate and adaptive compartments. One investigation revealed that DMF increases monocytic reactive oxygen species and modulates the Nrf2 redox regulator, distinguishing responders from non-responders and identifying a NOX3 genetic variant correlated with clinical benefit. Another work demonstrated that DMF suppresses IL-17-producing CD8+ T cells by engaging the PI3K-AKT-FOXO1-T-BET axis, inducing chromatin remodelling at the Il17 locus and thereby shifting the balance towards a less proinflammatory T-cell phenotype. These findings clarify the molecular underpinnings of DMF’s dual action on myeloid and lymphoid cells and suggest candidate biomarkers to inform therapeutic decision-making.

Immunomodulatory Therapies in Multiple Sclerosis Management publication trend

The graph below shows the total number of articles in immunomodulatory therapies in multiple sclerosis management across all publications each year (not limited to Nature Index journals).

Technical terms

Immunomodulatory therapy: Treatment designed to alter the immune response, either by suppression of pathogenic elements or enhancement of regulatory pathways.

Tolerogenic dendritic cell (tolDC): A dendritic cell engineered to present antigen in a way that induces immune tolerance rather than activation.

Immune reconstitution therapy (IRT): A strategy involving transient lymphocyte depletion followed by selective immune repopulation favouring regulatory cell subsets.

Nrf2: A transcription factor that controls antioxidant gene expression and maintains redox homeostasis under oxidative stress.

PI3K-AKT-FOXO1-T-BET pathway: A signalling cascade that influences T-cell differentiation by modulating transcriptional regulators and cytokine expression.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that function in cell signalling and can mediate antimicrobial and regulatory immune processes.

References

1. Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis. Journal of Clinical Investigation (2024).
2. Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy. Journal of Neuroinflammation (2023).
3. Long‐term peripheral immune cell profiling reveals further targets of oral cladribine in MS. Annals of Clinical and Translational Neurology (2020).
4. Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes. Nature Communications (2019).
5. IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis. Nature Communications (2019).