Abstract
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.
Highlights
Brain injury from ischemic or hemorrhagic stroke results in tissue destruction in the involved brain regions and eventually loss of motor function
EPO is commonly known for regulating red blood cell production in patients with anemia [8,9], while granulocyte-colony stimulating factor (G-CSF) is generally known for acting on CD34+ hematopoietic stem cells to stimulate neutrophil progenitor proliferation and differentiation in patients with neutropenia, as well as mobilizing transplanted bone marrow stem cells in patients with hematological malignancies such as multiple myeloma [10,11]
Based on these previous reports showing the therapeutic advantages of an EPO and G-CSF combination [30,33], we evaluated whether EPO+G-CSF combination therapy safely yielded hematological and functional improvement in stroke patients
Summary
Brain injury from ischemic or hemorrhagic stroke results in tissue destruction in the involved brain regions and eventually loss of motor function. Pharmacological treatment using multiple drugs such as erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) has been introduced in clinical trials for stroke patients [1,2,3,4,5,6,7]. Hematopoietic growth factors such as EPO and G-CSF have been utilized to increase circulating blood cells, including red blood cells, white blood cells, and platelets, by stimulating bone marrow production. De La Peña et al [20] suggested that the co-administration of G-CSF as an adjunctive therapy with umbilical cord blood cell transplantation could overcome the therapeutic limitations of a single therapy by enhancing neuroprotective interactions in animal models
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