Evolution of Ms Therapies: From Conventional Disease Modifying Therapies[DMTS] to Targeted, Neurorestorative and Car-T Cell Therapy

ABSTRACT: MS is a chronic inflammatory and neurodegenerative disease of the CNS, characterized by demyelination, axonal injury, and progressive neurological disability. Conventional DMTs reduce relapses and peripheral inflammation but have limited efficacy against progressive disability, compartmentalized CNS inflammation, neurodegeneration, and impaired remyelination. This review outlines the shift from conventional inflammatory control towards mechanism-based strategies that address these unmet needs. BTK inhibitors provide dual modulation of B-cell and myeloid-cell signalling, and CNS-penetrant agents may access compartmentalized CNS inflammation. Neuroprotective and remyelination strategies aim to preserve axonal integrity and restore myelin by targeting OPCs and the lesion microenvironment. CAR-T therapy is an emerging immune-resetting strategy that targets pathogenic B-cell populations and may provide durable immune reconstitution. These approaches face challenges of long-term safety, limited clinical evidence, progressive disease, CNS accessibility, target selection, treatment complexity, cost, and disease heterogeneity. Future MS management will likely involve earlier, individualized, and biomarker-guided strategies combining targeted immune modulation, neuroprotection, and CNS repair. The therapeutic evolution of MS thus extends beyond suppression of peripheral inflammation towards targeting pathogenic immunity, compartmentalized CNS inflammation, neurodegeneration, and impaired remyelination.