[Update on pathophysiologic and immunotherapeutic approaches for the treatment of multiple sclerosis].
Multiple sclerosis (MS) is a chronic disabling disease with significant implications for patients and society. The individual disease course is difficult to predict due to the heterogeneity of clinical presentation and of radiologic and pathologic findings. Although its etiology still remains unknown, the last decade has brought considerable understanding of the underlying pathophysiology of MS. In addition to its acceptance as a prototypic inflammatory autoimmune disorder, recent data reveal the importance of primary and secondary neurodegenerative mechanisms such as oligodendrocyte death, axonal loss, and ion channel dysfunction. The deepened understanding of its immunopathogenesis and the limited effectiveness of currently approved disease-modifying therapies have led to a tremendous number of trials investigating potential new drugs. Emerging treatments take into account the different immunopathological mechanisms and strategies, to protect against axonal damage and promote remyelination. This review provides a compilation of novel immunotherapeutic strategies and recently uncovered aspects of known immunotherapeutic agents. The pathogenetic rationale of these novel drugs for the treatment of MS and accompanying preclinical and clinical data are highlighted.
Kleinschnitz
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Neurologische Klinik und Poliklinik, Universitätsklinikum, Josef-Schneider-Strasse 11, 97080, Würzburg, Germany.
Meuth
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Kieseier
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Wiendl
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D001324:Autoantigens / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000502:physiology; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005609:Free Radicals; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D012183:Retrograde Degeneration / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001324:Autoantigens; D015938:Complement Membrane Attack Complex; D016207:Cytokines; D005609:Free Radicals; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents