Antioxidant treatment of patients with Friedreich ataxia - Four-year follow-up
Antioxidant treatment of patients with Friedreich ataxia - Four-year follow-up
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DOI：
10.1001/archneur.62.4.621
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Cooper, JM
中科院分区：
文献类型：
--
作者：
Hart, PE;Lodi, R;Cooper, JM
背景资料：线粒体呼吸链功能下降和氧化应激增加与弗里德赖希共济失调（FRDA）的发病机制有关，这增加了能量增强和抗氧化疗法可能是有效治疗FRDA的可能性。目的：评估抗氧化剂和线粒体增强联合疗法对FRDA生物能量学和临床过程的长期疗效。设计：超过47个月的开放标签先导试验。患者：77例临床和遗传定义的FRDA患者。干预：联合辅酶Q（10）（400毫克/天）和维生素E（2100 IU/d）治疗10例FRDA患者超过47个月。主要结果指标：使用超声心动图和国际协作共济失调评定量表进行临床评估，并使用磷P31磁共振波谱评估心脏和骨骼肌生物能量学。在整个47个月的治疗中，心脏和骨骼肌生物能量学得到了显著改善。超声心动图数据显示在35个月和47个月时间点缩短分数显著增加。与77例FRDA患者的横断面数据比较表明，在试验期间，7例患者的总国际合作共济失调评定量表和动力学评分的变化优于预测，但姿势和步态以及手灵巧度评分的进展与预测一致。这种疗法导致线粒体能量合成的持续改善，这与某些临床疾病进展的减缓有关。功能和心脏功能的显着改善。
Background: Decreased mitochondrial respiratory chain function and increased oxidative stress have been implicated in the pathogenesis of Friedreich ataxia (FRDA), raising the possibility that energy enhancement and antioxidant therapies may be an effective treatment.Objective: To evaluate the long-term efficacy of a combined antioxidant and mitochondrial enhancement therapy on the bioenergetics and clinical course of FRDA.Design: Open-labeled pilot trial over 47 months.Patients: Seventy-seven patients with clinical and genetically defined FRDA.Intervention: A combined coenzyme Q(10) (400 mg/d) and vitamin E (2100 IU/d) therapy of 10 patients with FRDA over 47 months.Main Outcome Measures: Clinical assessment using echocardiography and the International Cooperative Ataxia Rating Scale and cardiac and skeletal muscle bioenergetics, as assessed using phosphorus P 31 magnetic resonance spectroscopy.Results: There was a significant improvement in cardiac and skeletal muscle bioenergetics that was maintained throughout the 47 months of therapy. Echocardiographic data revealed significantly increased fractional shortening at the 35- and 47-month time points. Comparison with cross-sectional data from 77 patients with FRDA indicated the changes in total International Cooperative Ataxia Rating Scale and kinetic scores over the trial period were better than predicted for 7 patients, but the posture and gait and hand dexterity scores progressed as predicted.Conclusion: This therapy resulted in sustained improvement in mitochondrial energy synthesis that was associated with a slowing of the progression of certain clinical features and a significant improvement in cardiac function.