Boesch Sylvia, Sturm Brigitte, Hering Sascha, Scheiber-Mojdehkar Barbara, Steinkellner Hannes, Goldenberg Hans, Poewe Werner
Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Mov Disord. 2008 Oct 15;23(13):1940-4. doi: 10.1002/mds.22294.
In a "proof-of-concept" study, we demonstrated that recombinant human erythropoietin (rhuEPO) increases frataxin levels in Friedreich's ataxia (FRDA) patients. We now report a 6-month open-label clinical pilot study of safety and efficacy of rhuEPO treatment in FRDA. Eight adult FRDA patients received 2.000 IU rhuEPO thrice a week subcutaneously. Clinical outcome measures included Ataxia Rating Scales. Frataxin levels and indicators for oxidative stress were assessed. Hematological parameters were monitored biweekly. Scores in Ataxia Rating Scales such as FARS (P = 0.0063) and SARA (P = 0.0045) improved significantly. Frataxin levels increased (P = 0.017) while indicators of oxidative stress such as urine 8-OHdG (P = 0.012) and peroxide levels decreased (P = 0.028). Increases in hematocrit requiring phlebotomies occurred in 4 of 8 patients. In this explorative open-label clinical pilot study, we found an evidence for clinical improvement together with a persistent increase of frataxin levels and a reduction of oxidative stress parameters in patients with FRDA receiving chronic treatment with rhuEPO. Safety monitoring with regular blood cell counts and parameters of iron metabolism is a potential limitation of this approach.
在一项“概念验证”研究中，我们证明重组人促红细胞生成素（rhuEPO）可提高弗里德赖希共济失调（FRDA）患者体内的铁调素水平。我们现在报告一项关于rhuEPO治疗FRDA安全性和有效性的为期6个月的开放标签临床试验。8名成年FRDA患者每周皮下注射3次2000国际单位的rhuEPO。临床结局指标包括共济失调评定量表。评估了铁调素水平和氧化应激指标。每两周监测一次血液学参数。共济失调评定量表中的评分，如FARS（P = 0.0063）和SARA（P = 0.0045）显著改善。铁调素水平升高（P = 0.017），而氧化应激指标如尿8-羟基脱氧鸟苷（P = 0.012）和过氧化物水平降低（P = 0.028）。8名患者中有4名出现需要放血治疗以降低血细胞比容的情况。在这项探索性开放标签临床试验中，我们发现接受rhuEPO长期治疗的FRDA患者有临床改善的证据，同时铁调素水平持续升高，氧化应激参数降低。通过定期血细胞计数和铁代谢参数进行安全监测是这种方法的一个潜在限制。
