NOVEL THERAPIES TO HALT DEMYELINATION IN PROGRESSIVE MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is a complex autoimmune and progressive neurodegenerative disease that affects the central nervous system. It is characterized by demyelination due to oligodendrocyte dysfunction, which leads to myelin damage and subsequent axonal degeneration, impairing the efficient transmission of electrical impulses along nerves. MS typically follows one of several disease courses, including relapsing-remitting, primary progressive, or secondary progressive forms. Current treatments for MS are primarily immunomodulatory, designed to reduce inflammation and slow disease progression. However, effective treatments that directly promote myelin repair or provide neuroprotection remain lacking, particularly for the progressive forms of the disease. In this study, we investigated novel therapeutic approaches targeting progressive MS. To this end, we induced experimental autoimmune encephalomyelitis (EAE) in young adult female mice, a well-established model of MS. Two weeks after disease induction, animals were treated with various antagonists targeting AMPA, NMDA, and P2X7 receptors. Neurological scores were daily recorded to monitor disease progression and treatment response. After two additional weeks of treatment, mice were sacrificed, and their spinal cord tissues were collected for analysis. To evaluate the functional integrity of the corticospinal tract, we measured conduction latencies. Treated animals displayed significantly shorter conduction latencies, indicative of improved neural transmission. Complementing these findings, immunocytochemical analysis revealed a reduction in the lesioned area in treated mice, suggesting a potential neuroprotective or anti-inflammatory effect of the receptor antagonists. Together, these results offer promising insights into the potential of combined therapeutic strategies approaches to mitigate demyelination and promote neuroprotection in progressive MS.