BRAIN and NERVE Shinkei Kenkyu no Shinpo Volume 71, Issue 6 (June 2019)

Current Status and Prospects of Complement-Targeting Therapy for Neuromyelitis Optica Hiroshi Kuroda 1 , Kazuo Fujihara 2 1Department of Neurology, Tohoku University School of Medicine 2Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine Keyword: アクアポリン4抗体 , 免疫介在性アストロサイトパチー , 補体活性化 , 膜侵襲複合体 , エクリズマブ , aquaporin-4 IgG , immune-mediated astrocytopathy , complement activation , membrane attack complex , eculizumab pp.573-580
Published Date 2019/6/1
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Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and long myelitis; and is associated with aquaporin-4 immunoglobulin-G (AQP4-IgG), an autoantibody directed against aquaporin-4 (AQP4), which is an astrocytic water channel protein. Until recent years, the treatment of NMO has mainly focused on the suppression of lymphocytes and depletion of autoantibodies. However, several studies on the pathogehesis of the disease in human pathology, cultured cells, and animal models have revealed that astrocyte injury in NMO is mainly caused by the complement-dependent cytotoxicity following AQP4-IgG binding to AQP4. Moreover, complement-targeting therapy has recently been translated into practical applications in several hematological disorders. and similary, also in the cases of NMO. In this article, we review the relevance of the complement system in the pathogenesis of NMO. Additionally, we review the current status and prospects of the complement-targeting therapy for NMO, including the clinical trials of eculizumab and C1 inhibitor for NMO, and the experimental studies on C1 inhibition by monoclonal antibodies.

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BRAIN and NERVE-神経研究の進歩
71巻6号 (2019年6月)
電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院