Department of Neurology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Arch Immunol Ther Exp (Warsz). 2010 Oct;58(5):325-33. doi: 10.1007/s00005-010-0094-x. Epub 2010 Jul 31.
Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS); it affect millions of patients worldwide and the number of patients is on the rise. Current treatment options are fairly limited and there is a strong unmet need for disease-targeted therapies for MS. The most widely accepted hypothesis for the pathogenesis of MS is that it is a primary autoimmune disease in which myelin-specific T cells play a central role in the progression of demyelination. According to this hypothesis, a powerful immune suppression or a reconstruction of the immune system to abrogate disease-specific leukocytes early in the development of the disease is expected to halt or even reverse the disease, since remyelination is an exceptionally efficient regenerative process in the CNS. However, recent neuropathological studies have provided evidence of primary oligodendrogliopathy as a cause of demyelination, suggesting that immune reactions may be a mere secondary event in the course of MS. On the other hand, some recent clinical trial results of new immune-suppressive treatments showed a nearly complete blockade of relapses and significant, albeit incomplete, neurological improvement. Therefore, which hypothesis--autoimmunity or oligodendrogliopathy--lights the correct path to a "cure" for MS?
多发性硬化症（MS）是中枢神经系统（CNS）最常见的炎症性脱髓鞘疾病；它影响着全球数以百万计的患者，且患者人数还在不断增加。目前的治疗选择相当有限，因此非常需要针对 MS 的疾病靶向疗法。MS 发病机制最广为接受的假说为，它是一种主要的自身免疫性疾病，其中髓鞘特异性 T 细胞在脱髓鞘进展中起着核心作用。根据这一假说，在疾病发展的早期，强有力的免疫抑制或重建免疫系统以消除疾病特异性白细胞，有望阻止甚至逆转疾病，因为髓鞘再生是 CNS 中一种异常有效的再生过程。然而，最近的神经病理学研究提供了原发性少突胶质细胞病是脱髓鞘原因的证据，这表明免疫反应可能只是 MS 病程中的一个次要事件。另一方面，一些新的免疫抑制治疗的最新临床试验结果表明，复发几乎完全被阻断，且神经功能有显著但不完全的改善。因此，哪种假说——自身免疫或少突胶质细胞病——指明了 MS“治愈”的正确道路？
