Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX 75216, USA.
J Neurol Sci. 2009 Dec;287 Suppl 1:S30-6. doi: 10.1016/S0022-510X(09)71298-5.
Multiple sclerosis is a chronic disease confined to the central nervous system. Its pathological hallmarks are neuroinflammation, de- and re-myelination, neurodegeneration and astrogliosis. The aetiology of multiple sclerosis is unknown, although a growing body of evidence supports an autoimmune pathogenesis triggered by environmental factors in genetically susceptible individuals. It is therefore perhaps unsurprising that immunomodulatory therapies have now been the mainstay of pharmacotherapy and the focus for the search for a cure for many decades. Currently, clinicians have access to two distinct treatment strategies, namely general immunomodulation or immunosuppression. During the last two decades, several immunomodulatory agents and one immunosuppressant drug have been shown to be effective in clinical trials and have been approved on this basis for the treatment of multiple sclerosis. Current drugs offer well-established safe and effective therapeutic agents for multiple sclerosis in both the short and long term. More recently, growing knowledge of specific anatomical, cellular and molecular targets that play critical roles in the inflammatory cascade of multiple sclerosis have shifted the focus of drug development towards specific targets. Future multiple sclerosis therapies arising from this research may offer better suppression of disease activity, but may be associated with potentially severe side-effects in some patients that may be difficult to manage. In the near future, better understanding of the pathogenesis of multiple sclerosis will probably allow the development of even more effective agents for all clinical phenotypes of the disease. Future therapeutic agents will also have to be designed to address the neurodegenerative component of the physiopathology of multiple sclerosis.
多发性硬化症是一种局限于中枢神经系统的慢性疾病。其病理特征是神经炎症、脱髓鞘和再髓鞘、神经退行性变和星形胶质细胞增生。多发性硬化症的病因尚不清楚，尽管越来越多的证据支持环境因素在遗传易感个体中引发自身免疫发病机制。因此，免疫调节疗法现已成为许多年来药物治疗的主要方法，并成为寻找治愈方法的焦点，这也许并不奇怪。目前，临床医生有两种不同的治疗策略，即一般免疫调节或免疫抑制。在过去的二十年中，已经证明几种免疫调节剂和一种免疫抑制剂在临床试验中有效，并在此基础上被批准用于治疗多发性硬化症。目前的药物在短期和长期内为多发性硬化症提供了成熟、安全和有效的治疗药物。最近，对特定解剖、细胞和分子靶点在多发性硬化症炎症级联反应中发挥关键作用的认识不断提高，使药物开发的重点转向了特定靶点。由此产生的未来多发性硬化症疗法可能会更好地抑制疾病活动，但在某些患者中可能会出现严重的潜在副作用，这可能难以管理。在不久的将来，对多发性硬化症发病机制的更好理解可能会为所有疾病的临床表型开发出更有效的药物。未来的治疗药物还必须设计用于解决多发性硬化症病理生理学中的神经退行性成分。
