Schulz Jörg B, Di Prospero Nicholas A, Fischbeck Kenneth
Department of Neurology, University Medical Centre, RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
J Neurol. 2009 Mar;256 Suppl 1(0 1):42-5. doi: 10.1007/s00415-009-1008-x.
Several reports in the literature describe the effects of low-dose (5 mg/kg/day) idebenone in significantly reducing cardiac hypertrophy in patients with Friedreich ataxia. However, the effects of idebenone on neurological function have not been reliably determined in these studies; when neurological parameters were reported, results were often inconclusive, usually because of subject heterogeneity and lack of adequate statistical power. In two of these studies, some patients showed beneficial effects of idebenone on their cardiomyopathy only when the dose was increased, prompting the systematic investigation of higher doses of idebenone. Following a phase 1 dose escalation study, a phase 2 tolerability and efficacy trial with low, intermediate, and high doses of idebenone was conducted. The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms. On the basis of these results, two phase 3 trials have been initiated, one in the United States with young ambulatory patients and one in Europe without limits on age and disease severity.
文献中的几篇报道描述了低剂量（5毫克/千克/天）艾地苯醌在显著减轻弗里德赖希共济失调患者心脏肥大方面的作用。然而，在这些研究中，艾地苯醌对神经功能的影响尚未得到可靠确定；当报告神经学参数时，结果往往没有定论，通常是由于受试者的异质性和缺乏足够的统计效力。在其中两项研究中，一些患者仅在剂量增加时才显示出艾地苯醌对其心肌病的有益作用，这促使对更高剂量的艾地苯醌进行系统研究。在一项1期剂量递增研究之后，进行了一项2期艾地苯醌低、中、高剂量耐受性和疗效试验。结果表明，中高剂量艾地苯醌治疗对神经症状有有益作用。基于这些结果，已启动两项3期试验，一项在美国针对年轻的非卧床患者，另一项在欧洲对年龄和疾病严重程度没有限制。
