Epigenetic and genetic insights for tailored therapeutic strategies in multiple sclerosis.

Multiple sclerosis (MS) is a complex neurological disorder with inflammation, demyelination, and neurodegeneration in the CNS. Disease-modifying therapies (DMTs) exist, but their efficacy is limited by MS's varied nature, highlighting the need for personalized treatments. From January 2009 to March 2025, a literature search across PubMed, Scopus, Web of Science, and Google Scholar identified over 200 multiple sclerosis (MS) genetic loci. HLA-DRB1*15:01 is a key genetic risk factor, alongside significant environmental contributors such as Epstein-Barr virus infection, smoking, and vitamin D deficiency. Epigenetic modifications, such as DNA methylation and non-coding RNAs, mediate the interaction between genetic predisposition and environmental factors. Altered methylation patterns in genes like FOXP3 and IL-10 disrupt immune regulation, exacerbating disease progression. Emerging biomarkers such as CHI3L1, miR-155, and IL-10 methylation patterns have shown potential for diagnosis and prognosis. Multi-omics strategies and artificial intelligence (AI) offer innovative solutions for integrating these biomarkers into clinical practice. Personalized therapy options, such as low-dose IL-2 and JAK-STAT pathway inhibitors, highlight the potential of precision medicine in enhancing treatment outcomes. This synthesis identifies inconsistencies and methodological limitations in current research, proposing a roadmap for pathway-specific therapies based on integrated genetic-epigenetic profiling.