Giannetti Paolo, Niccolini Flavia, Nicholas Richard
Centre for Neurosciences, Division of Experimental Medicine, Department of Medicine, Imperial College, London, UK,
University of Rome "Sapienza", Department of Neurology and Psychiatry, Rome, Italy.
Degener Neurol Neuromuscul Dis. 2012 Sep 28;2:119-132. doi: 10.2147/DNND.S35790. eCollection 2012.
Multiple sclerosis (MS) arises from an immune attack on the central nervous system producing demyelination and axonal loss. Clinically the relapsing-remitting course is characterized by subacute onset of neurological symptoms usually with partial or complete recovery, while the progressive course, predominant in the later stages, is characterized by progressive disability in the absence of relapses. A number of disease-modifying treatments have been developed and are increasingly effective at targeting relapses. Early injectable therapies such as interferon and glatiramer acetate are only partially effective, but have a good safety record. Recently, natalizumab, an intravenous therapy, demonstrated increased effectiveness, but side effects complicate its use. The first oral therapy offering good efficacy and convenience, fingolimod, was approved in USA in 2010 and Europe in 2011. BG-12 is a potential novel oral therapy for MS, which has previously been used as a different formulation for psoriasis. It has anti-inflammatory and neuroprotective actions in vitro, which makes it a promising candidate for future therapies. Phase II studies showed that BG-12 reduced MRI inflammatory activity over placebo, which was confirmed in two Phase III studies indicating immune modulation may be its principal action rather than neuroprotection. In these studies, BG-12 reduced relapse rates consistently with variable effects on progression and few serious adverse events. With its favorable efficacy-tolerability profile, BG-12 could offer a substantial step forward for the care for subjects affected by relapsing MS.
多发性硬化症(MS)是由针对中枢神经系统的免疫攻击引起的,会导致脱髓鞘和轴突损失。临床上,复发缓解型病程的特点是神经症状亚急性发作,通常部分或完全恢复,而在后期占主导的进展型病程则表现为在无复发情况下的进行性残疾。已经开发出多种疾病修正治疗方法,并且在针对复发方面越来越有效。早期的注射疗法,如干扰素和醋酸格拉替雷,仅部分有效,但安全性良好。最近,静脉注射疗法那他珠单抗显示出更高的疗效,但副作用使其使用变得复杂。第一种具有良好疗效和便利性的口服疗法芬戈莫德,于2010年在美国获批,2011年在欧洲获批。BG-12是一种潜在的新型MS口服疗法,此前曾以不同配方用于治疗银屑病。它在体外具有抗炎和神经保护作用,这使其成为未来治疗的有希望的候选药物。II期研究表明,与安慰剂相比,BG-12可降低MRI炎症活动,这在两项III期研究中得到证实,表明免疫调节可能是其主要作用而非神经保护作用。在这些研究中,BG-12持续降低复发率,对疾病进展有不同影响,且严重不良事件较少。凭借其良好的疗效-耐受性特征,BG-12可为复发型MS患者的护理带来实质性进展。