Rustin Pierre, Rötig Agnès, Munnich Arnold, Sidi Daniel
Unité de Recherches sur les Handicaps Génétiques de l'Enfant (INSERM U393), Hôpital Necker-Enfants Malades, Paris, France.
Free Radic Res. 2002 Apr;36(4):467-9. doi: 10.1080/10715760290021333.
Friedreich's ataxia (FRDA) is a neuro-degenerative disease causing limb and gait ataxia and hypertrophic cardiomyopathy. It results from a triplet expansion in the first intron of the frataxin gene encoding a mitochondrial protein of yet unknown function. Cells with low frataxin content display generalized deficiency of mitochondrial iron-sulfur cluster-containing proteins, which presumably denotes overproduction of superoxide radicals in these organelles. Idebenone, a short-chain quinone, may act as a potent free radical scavenger protecting mitochondria against oxidative stress. We therefore carried out an open trial of idebenone (oral supplementation; 5mg/kg/day) in a large series of FRDA patients and followed their left ventricular mass and function. Consistent and definitive worsening being observed in the natural course of the disease and cardiac hypertrophy having no chance of spontaneous reversal and to be subject to a placebo effect, the patient's heart status before and after the treatment was used to unambiguously establish the effect of the drug. After six months, heart ultrasound revealed more than 20% reduction of left ventricular mass in about half of the patients (p < 0.001) and no significant change in the other half. Since any measurable reversion of this pathogenic trait is highly significant, this demonstrates the efficiency of idebenone in controlling heart hypertrophy in FRDA. Owing to the absence of side effects of the drug, idebenone (up to 15mg/kg/day) should be prescribed for FRDA patients continuously as early as possible.
弗里德赖希共济失调（FRDA）是一种神经退行性疾病，可导致肢体和步态共济失调以及肥厚型心肌病。它是由编码一种功能尚不清楚的线粒体蛋白的铁调素基因的第一个内含子中的三联体扩增引起的。铁调素含量低的细胞表现出线粒体含铁硫簇蛋白的普遍缺乏，这可能表明这些细胞器中超氧自由基的过量产生。艾地苯醌是一种短链醌类，可能作为一种有效的自由基清除剂，保护线粒体免受氧化应激。因此，我们对大量FRDA患者进行了艾地苯醌的开放试验（口服补充；5mg/kg/天），并跟踪他们的左心室质量和功能。由于在疾病的自然病程中观察到持续且明确的恶化，且心脏肥大没有自发逆转的机会且会受到安慰剂效应的影响，因此使用患者治疗前后的心脏状况来明确确定药物的效果。六个月后，心脏超声显示约一半患者的左心室质量减少了20%以上（p<0.001），另一半患者无明显变化。由于这种致病特征的任何可测量的逆转都具有高度显著性，这证明了艾地苯醌在控制FRDA患者心脏肥大方面的有效性。由于该药物没有副作用，应尽早持续为FRDA患者开具艾地苯醌（最高15mg/kg/天）。
