Neurological Effects of Recombinant Human Erythropoietin in Friedreich's Ataxia: A Clinical Pilot Trial
Neurological Effects of Recombinant Human Erythropoietin in Friedreich's Ataxia: A Clinical Pilot Trial
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DOI：
10.1002/mds.22294
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发表时间：
2008-10-15
影响因子：
8.6
通讯作者：
Poewe, Werner
中科院分区：
文献类型：
--
作者：
Boesch, Sylvia;Sturm, Brigitte;Poewe, Werner
在一项“概念验证”研究中，我们证明了重组人促红细胞生成素（rhuEPO）增加弗里德赖希共济失调（FRDA）患者的共济失调蛋白水平。我们现在报告一项为期6个月的开放标签临床试验研究，研究rhuEPO治疗FRDA的安全性和有效性。8例成人FRDA患者接受2.000 IU rhuEPO皮下注射，每周3次。临床结局指标包括共济失调评定量表。评估Frataxin水平和氧化应激指标。每两周监测一次血液学参数。共济失调评定量表评分，如法尔斯（P = 0.0063）和SARA（P = 0.0045）显著改善。Frataxin水平增加（P = 0.017），而氧化应激指标如尿8-OHdG（P = 0.012）和过氧化物水平降低（P = 0.028）。8例患者中有4例发生红细胞压积升高，需要进行静脉切开术。在这项探索性的开放标签临床试点研究中，我们发现了接受rhuEPO长期治疗的FRDA患者的临床改善以及共济失调蛋白水平持续增加和氧化应激参数降低的证据。定期血细胞计数和铁代谢参数的安全性监测是这种方法的潜在局限性。(C)2008运动障碍协会
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. (C) 2008 Movement Disorder Society