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Multiple-Sklerose-Update zur Pathophysiologie und neuen immuntherapeutischen Ansätzen

Update on pathophysiologic and immunotherapeutic approaches for the treatment of multiple sclerosis

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Zusammenfassung

Die Multiple Sklerose (MS) ist eine chronische Erkrankung, die überwiegend junge Erwachsene betrifft und zu bleibender Behinderung führen kann. Obwohl die Ätiologie der MS noch immer unbekannt ist, haben die vergangenen 10 Jahre beträchtliche Erfolge im Verständnis der zugrunde liegenden Pathophysiologie gebracht. Während die MS als Prototyp einer entzündlichen Autoimmunerkrankung des zentralen Nervensystems (ZNS) angesehen wird, unterstreichen jüngste Daten die Wichtigkeit primärer und sekundärer neurodegenerativer Mechanismen. Die Zulassung des ersten monoklonalen Antikörpers in der neurologischen Therapie, Natalizumab (Tysabri®), verdeutlicht die rasante Weiterentwicklung im Feld. Neuere Behandlungsstrategien zielen insbesondere auch darauf ab, axonalen Schaden zu begrenzen (Axon-/Neuroprotektion) und/oder die Remyelinisierung zu fördern. Der Übersichtsartikel referiert neue Erkenntnisse in der Pathophysiologie der MS; im 2. Teil werden die wichtigsten laufenden oder kürzlich abgeschlossenen klinischen Therapiestudien zusammengestellt.

Summary

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.

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  1. Neurologische Klinik und Poliklinik, Universitätsklinikum, Josef-Schneider-Straße 11, 97080, Würzburg, Deutschland

    C. Kleinschnitz, S.G. Meuth &  H. Wiendl

  2. Neurologische Klinik und Poliklinik , Universitätsklinikum, Düsseldorf, Deutschland

    B.C. Kieseier

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Kleinschnitz, C., Meuth, S., Kieseier, B. et al. Multiple-Sklerose-Update zur Pathophysiologie und neuen immuntherapeutischen Ansätzen. Nervenarzt 78, 883–911 (2007). https://doi.org/10.1007/s00115-007-2261-9

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