Huang DeRen, Rae-Grant Alexander
Center for Multiple Sclerosis, Neurology and Neuroscience Associates, Inc., Akron, OH 44302, USA.
Cent Nerv Syst Agents Med Chem. 2009 Mar;9(1):20-31. doi: 10.2174/187152409787601923.
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS). It is characterized by episodic and progressive neurological dysfunction resulting from inflammatory and autoimmune reactions, myelin loss, conduction block, oligodendrocyte pathology, gliosis, and axonal loss in CNS. Recent years have witnessed advances in better understanding the immune pathogenesis of MS, prompted by animal models, human pathological observations and MRI studies. There have been significant changes in the therapeutic regimens in MS, with an emphasis on preventative treatment of an ongoing disease process. Agents in use and in the research pipeline have mechanisms that act on various anti-inflammatory and immunomodulatory properties, including blocking leukocyte migration into CNS and targeting chemoattraction. In addition, recent studies on the neurodegenerative components of MS have directed therapeutic trials to neuroprotection and neurorestoration. In this paper, we summarize the current understanding of the mechanisms of approved pharmacological agents and review the putative mechanisms and status of some important agents in clinical phase two or three trials in MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）疾病。其特征是由炎症和自身免疫反应、髓鞘丢失、传导阻滞、少突胶质细胞病变、胶质增生以及中枢神经系统轴突丢失导致的发作性和进行性神经功能障碍。近年来，在动物模型、人体病理学观察和MRI研究的推动下，人们对MS免疫发病机制的认识取得了进展。MS的治疗方案发生了重大变化，重点是对正在进行的疾病进程进行预防性治疗。正在使用和处于研发阶段的药物具有作用于各种抗炎和免疫调节特性的机制，包括阻止白细胞迁移到中枢神经系统以及靶向趋化作用。此外，最近对MS神经退行性成分的研究已将治疗试验导向神经保护和神经修复。在本文中，我们总结了对已批准药物作用机制的当前认识，并回顾了MS临床二、三期试验中一些重要药物的假定机制和现状。
