Kleinschnitz C, Meuth S G, Kieseier B C, Wiendl H
Neurologische Klinik und Poliklinik, Universitätsklinikum, Josef-Schneider-Strasse 11, 97080, Würzburg, Germany.
Nervenarzt. 2007 Aug;78(8):883-911. doi: 10.1007/s00115-007-2261-9.
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.
多发性硬化症(MS)是一种慢性致残性疾病,对患者和社会都有重大影响。由于临床表现以及放射学和病理学发现的异质性,个体疾病进程难以预测。尽管其病因仍不明确,但在过去十年中,人们对MS的潜在病理生理学有了相当深入的了解。除了被公认为一种典型的炎症性自身免疫性疾病外,最近的数据还揭示了原发性和继发性神经退行性机制的重要性,如少突胶质细胞死亡、轴突丢失和离子通道功能障碍。对其免疫发病机制的深入理解以及目前批准的疾病修饰疗法的有限有效性,导致了大量研究潜在新药的试验。新兴疗法考虑了不同的免疫病理机制和策略,以防止轴突损伤并促进髓鞘再生。本综述汇编了新型免疫治疗策略以及已知免疫治疗药物最近发现的方面。重点介绍了这些用于治疗MS的新药的发病学原理以及相关的临床前和临床数据。