Neuhaus Oliver, Stüve Olaf, Zamvil Scott S, Hartung Hans-Peter
Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
CNS Drugs. 2005;19(10):833-41. doi: 10.2165/00023210-200519100-00003.
The disease-modifying agents currently used in the treatment of multiple sclerosis (MS) are not completely effective and are associated with adverse effects and high costs. Thus, alternative treatment options are highly desirable. HMG-CoA reductase inhibitors (statins), widely prescribed as cholesterol-lowering agents, may be a future treatment option for MS--either in an add-on therapy regimen or alone--as they have been shown to exhibit potent immunomodulatory effects. Several recent reports have demonstrated that HMG-CoA reductase inhibitors prevent and reverse chronic and relapsing experimental autoimmune encephalomyelitis, an animal model of MS. Furthermore, in vitro experiments with human immune cells have shown an immunomodulatory mode of action of HMG-CoA reductase inhibitors that is comparable to that of interferon-beta, an established treatment for MS. An open-label clinical trial assessing simvastatin treatment in patients with MS revealed a significant decrease in the number and volume of new lesions, as assessed using magnetic resonance imaging, and a favourable safety profile. A large multicentre, placebo-controlled phase II clinical trial assessing atorvastatin in patients with a clinically isolated syndrome (i.e. a single clinical event that is indicative of demyelination, and that predisposes to the development MS) has recently been initiated. However, prospective placebo-controlled trials of HMG-CoA reductase inhibitors in definite MS are difficult to perform because of ethical and financial issues. Furthermore, overly optimistic reports in the popular media, as well as the often uncontrolled access to HMG-CoA reductase inhibitors by patients with MS, complicate the evaluation of HMG-CoA reductase inhibitors as a realistic future treatment option for MS.
目前用于治疗多发性硬化症（MS）的病情改善药物并不完全有效，且伴有不良反应和高昂成本。因此，非常需要其他治疗选择。HMG-CoA还原酶抑制剂（他汀类药物）作为广泛使用的降胆固醇药物，可能成为MS未来的治疗选择——无论是作为附加治疗方案还是单独使用——因为它们已被证明具有强大的免疫调节作用。最近的几份报告表明，HMG-CoA还原酶抑制剂可预防和逆转慢性复发性实验性自身免疫性脑脊髓炎，这是一种MS的动物模型。此外，对人类免疫细胞进行的体外实验表明，HMG-CoA还原酶抑制剂的免疫调节作用模式与已确立的MS治疗药物干扰素-β相当。一项评估辛伐他汀治疗MS患者的开放标签临床试验显示，使用磁共振成像评估发现新病灶的数量和体积显著减少，且安全性良好。最近启动了一项大型多中心、安慰剂对照的II期临床试验，评估阿托伐他汀对临床孤立综合征患者（即单一临床事件提示脱髓鞘且易发展为MS）的疗效。然而，由于伦理和资金问题，对明确诊断为MS的患者进行HMG-CoA还原酶抑制剂的前瞻性安慰剂对照试验很难开展。此外，大众媒体过于乐观的报道，以及MS患者往往不受控制地获取HMG-CoA还原酶抑制剂，使得将HMG-CoA还原酶抑制剂评估为MS未来切实可行的治疗选择变得复杂。
