Shin Yoon-Kyum, Cho Sung-Rae
Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
Int J Mol Sci. 2016 Mar 30;17(4):463. doi: 10.3390/ijms17040463.
Erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) are known to have neuroprotective actions. Based on previous reports showing the synergistic effects of EPO+G-CSF combination therapy in experimental models, we investigated the safety of EPO+G-CSF combination therapy in patients with chronic stroke. In a pilot study, 3 patients were treated with EPO and G-CSF for 5 consecutive days, with follow-up on day 30. In an exploratory double-blind study, 6 patients were allocated to treatment with either EPO+G-CSF or placebo. Treatment was applied once a day for 5 days per month over 3 months. Participants were followed up for 6 months. To substantiate safety, vital signs, adverse events, and hematological values were measured on days 0, 5, and 30 in each cycle and on day 180. Functional outcomes were determined on day 0 and 180. In the laboratory measurements, EPO+G-CSF combination therapy significantly elevated erythropoietin, CD34⁺ hematopoietic stem cells, white blood cells, and neutrophils on day 5 of each cycle. There were no observations of serious adverse events. In the functional outcomes, the grip power of the dominant hand was increased in the EPO+G-CSF treatment group. In conclusion, this exploratory study suggests a novel strategy of EPO+G-CSF combination therapy for stroke patients.
已知促红细胞生成素（EPO）和粒细胞集落刺激因子（G-CSF）具有神经保护作用。基于先前报告显示EPO+G-CSF联合治疗在实验模型中的协同效应，我们研究了EPO+G-CSF联合治疗对慢性中风患者的安全性。在一项试点研究中，3例患者连续5天接受EPO和G-CSF治疗，并在第30天进行随访。在一项探索性双盲研究中，6例患者被分配接受EPO+G-CSF或安慰剂治疗。治疗每月每天应用1次，共5天，持续3个月。对参与者进行6个月的随访。为证实安全性，在每个周期的第0、5和30天以及第180天测量生命体征、不良事件和血液学值。在第0和180天确定功能结局。在实验室测量中，EPO+G-CSF联合治疗在每个周期的第5天显著提高了促红细胞生成素、CD34⁺造血干细胞、白细胞和中性粒细胞水平。未观察到严重不良事件。在功能结局方面，EPO+G-CSF治疗组优势手的握力增加。总之，这项探索性研究为中风患者提出了一种新的EPO+G-CSF联合治疗策略。
