Department of Neurology, Technische Universität München, Munich, Germany.
Curr Pharm Des. 2012;18(2):209-19. doi: 10.2174/138161212799040501.
Recent years have broadened the spectrum of therapeutic strategies and specific agents for treatment of multiple sclerosis (MS). While immune-modulating drugs remain the first-line agents for MS predominantly due to their benign safety profile, our growing understanding of key processes in initiation and progression of MS has pioneered development of new agents with specific targets. One concept of these novel drugs is to hamper migration of immune cells towards the affected central nervous system (CNS). The first oral drug approved for MS therapy, fingolimod inhibits egress of lymphocytes from lymph nodes; the monoclonal antibody natalizumab prevents inflammatory CNS infiltration by blocking required adhesion molecules. The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). All of these novel, highly effective agents are a substantial improvement in our therapeutic armamentarium; however, they have in common to potentially lower the abundance of immune cells within the CNS, thereby collaterally affecting immune surveillance within this well-controlled compartment. In this review, we aim to critically evaluate the risk/benefit ratio of therapeutic strategies in treatment of MS with a specific focus on infectious neurological side effects.
近年来,治疗多发性硬化症(MS)的治疗策略和特定药物的范围不断扩大。虽然免疫调节药物由于其良性的安全性仍然是 MS 的一线药物,但我们对 MS 发病和进展中关键过程的认识不断加深,为具有特定靶点的新型药物的开发奠定了基础。这些新型药物的一个概念是阻止免疫细胞向受影响的中枢神经系统(CNS)迁移。第一个批准用于 MS 治疗的口服药物芬戈莫德抑制淋巴细胞从淋巴结中迁出;单克隆抗体那他珠单抗通过阻断所需的粘附分子来阻止炎症性 CNS 浸润。第二个概念是使用高度特异性的单克隆抗体(如阿仑单抗(抗-CD52)或利妥昔单抗/奥瑞珠单抗(抗-CD20))从外周循环中清除 T 细胞和/或 B 细胞。所有这些新型的、高效的药物都是我们治疗武器库的重大改进;然而,它们都有一个共同点,即可能降低 CNS 内免疫细胞的丰度,从而对这个经过良好控制的区域内的免疫监视产生附带影响。在这篇综述中,我们旨在批判性地评估治疗 MS 的治疗策略的风险/效益比,特别关注感染性神经副作用。