Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
PLoS One. 2013 Jul 29;8(7):e69229. doi: 10.1371/journal.pone.0069229. Print 2013.
Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO) is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS). Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr) depletion and increased accumulation of inorganic phosphate (Pi) during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.
EU Clinical Trials Register2008-000040-13.
弗里德赖希共济失调（FRDA）是由 FXN 基因中的 GAA 重复扩展引起的，导致线粒体蛋白 frataxin 的表达减少。重组人促红细胞生成素（rhuEPO）被认为可以增加 frataxin 水平，改变线粒体功能，并改善 FRDA 患者的临床评分。本初步研究的目的是研究 FRDA 患者骨骼肌组织的线粒体代谢，并通过磷 31 磁共振波谱（31P MRS）检查 rhuEPO 给药的效果。7 名经基因确认的 FRDA 患者在接受 3000IU rhuEPO 治疗 8 周前后，使用休息-运动-恢复方案对小腿肌肉进行了 31P MRS。与对照组相比，FRDA 患者在递增运动中表现出更快的磷酸肌酸（PCr）耗竭和无机磷（Pi）的积累增加。在最大耗竭运动后，FRDA 患者可以看到较长时间的 PCR 再生和 Pi 下降速度减慢。作为线粒体 ATP 产生标志的 PCr 再生与呼吸链复合物 II/III 的活性和人口统计学值相关。PCr 和 Pi 动力学不受 rhuEPO 给药的影响。我们的研究结果证实了 FRDA 患者骨骼肌组织中线粒体功能障碍和运动不耐受，这是由于氧化磷酸化受损所致。经过 8 周 rhuEPO 暴露，MRS 并未显示 FRDA 患者骨骼肌组织中线粒体生物能量学得到改善。
欧盟临床试验注册处 2008-000040-13。
