Multiple Sclerosis: Unraveling the Neuropathology and Mechanisms of Neurodegeneration

Multiple Sclerosis (MS) is a debilitating autoimmune disease affecting the central nervous system, and has been the focus of intense research for the past 20 years. A better understanding of immune-related pathogenic mechanisms is necessary for the development of: (1) novel methods to monitor disease progression, (2) earlier diagnoses through unveiling new biomarkers, and (3) the invention of more effective and personalized MS treatments therapies. Several disease modifying treatments (e.g., natalizumab, fingolimod and beta interferons) have been approved for MS; however with no cure, the current treatment paradigm has shifted to the notion of ‘no evident disease activity’. While many of these Food and Drug Administration approved MS treatments have been shown to reduce the number of relapses and lesions, the paradox concerning MS treatments, namely the overuse of T cell activation as a target, necessitates the need for identifying entirely new contributors to disease pathology. MS pathogenesis has been associated with many theories, ranging from the release of proinflammatory cytokines from macrophages and microglial cells to B cell-derived demyelinating antibodies. As such, these hypotheses should be considered in addition to the role of T cells when developing novel MS treatment plans and identifying aligning biomarkers. Recently, clinical trials (ClinicalTrials.gov Identifier: NCT00040482, NCT00342134, and NCT00342134) investigating autologous hematopoietic stem cell transplantation have demonstrated success in MS. Future research should focus on identifying non-invasive biomarkers, such as blood concentrations of miRNAs, as an indication of underlying pathology and to aid in early diagnosis, tracking disease progression and identifying more effective and personalized MS treatments.