Treating primary-progressive multiple sclerosis: potential of ocrelizumab and review of B-cell therapies.

Degenerative Neurological and Neuromuscular Disease Pub Date : 2017-02-01 eCollection Date: 2017-01-01 DOI:10.2147/DNND.S100096

Jenny J Feng, Daniel Ontaneda

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Abstract

Multiple sclerosis (MS) therapy has evolved rapidly with an increased availability of several immunomodulating therapies over the past two decades. Disease-modifying therapies have proven to be effective in treating relapse-remitting MS (RRMS). However, clinical trials involving some of the same agents for secondary-progressive and primary-progressive MS (SPMS and PPMS) have been largely negative. The pathogenesis of progressive MS remains unclear, but B-cells may play a significant role in chronic compartmentalized inflammation, likely contributing to disease progression. Biologics targeted at B-cells, such as rituximab, are effective in treating RRMS. Ocrelizumab is a humanized monoclonal antibody to CD20⁺ B-cells that has shown positive results in PPMS with a significant reduction in disease progression. This review aims to discuss in detail the involvement of B-cells in MS pathogenesis, current progress of currently available and investigational biologics, with focus on ocrelizumab, and future prospects for B-cell therapy in PPMS.

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治疗原发性进展性多发性硬化症：奥克利珠单抗的潜力和 B 细胞疗法回顾。

多发性硬化症（MS）治疗在过去二十年中发展迅速，有越来越多的免疫调节疗法可供使用。事实证明，疾病调节疗法对治疗复发缓解型多发性硬化症（RRMS）非常有效。然而，针对继发性进展型多发性硬化症和原发性进展型多发性硬化症（SPMS 和 PPMS）的一些相同药物的临床试验结果大多为阴性。进展性多发性硬化症的发病机制仍不清楚，但 B 细胞可能在慢性分区炎症中扮演重要角色，很可能导致疾病进展。针对 B 细胞的生物制剂，如利妥昔单抗，可有效治疗 RRMS。Ocrelizumab 是一种针对 CD20+ B 细胞的人源化单克隆抗体，在 PPMS 中显示出积极的疗效，显著减少了疾病的进展。本综述旨在详细讨论 B 细胞在多发性硬化症发病机制中的参与、目前可用和在研生物制剂的进展（重点是奥克雷珠单抗）以及 PPMS 中 B 细胞疗法的未来前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Degenerative Neurological and Neuromuscular Disease

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