Erythropoietin therapy for acute stroke is both safe and beneficial

2002 | journal article; research paper. A publication of Göttingen

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​Erythropoietin therapy for acute stroke is both safe and beneficial​
Ehrenreich, H. ; Hasselblatt, M. ; Dembowski, C. ; Cepek, L. ; Lewczuk, P. ; Stiefel, M.   & Rustenbeck, H.-H.  et al.​ (2002) 
Molecular Medicine8(8) pp. 495​-505​.​

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Ehrenreich, Hannelore ; Hasselblatt, Martin ; Dembowski, Christoph ; Cepek, Lukas ; Lewczuk, Pjotr ; Stiefel, Michael ; Rustenbeck, Hans-Heino ; Breiter, Norbert ; Jacob, Sonja ; Knerlich, Friederike ; Bohn, Matthias ; Poser, Wolfgang ; Rüther, Eckart ; Kochen, Michael ; Gefeller, Olaf ; Gleiter, Christoph H. ; Wessel, Thomas C.; Ryck, Marc de; Itri, Loretta; Prange, Hilmar ; Cerami, Anthony; Brines, Michael; Siren, Anna-Leena 
Background: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man. Materials and Methods: The trial consisted of a safety part and an efficacy part. in the safety study, 13 patients received rhEPO intravenously (3.3 x 10(4) IU/50 m/130 min) once daily for the first 3 days after stroke. in the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age {.extbackslash}textless80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset {.extbackslash}textless8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of infarct size (sequential MRI evaluation using diffusion-weighted [DWI] and fluid-attenuated inversion recovery sequences [FLAIR]) and the damage marker S100ss. Results: No safety concerns were identified. Cerebrospinal fluid EPO increased to 60-100 times that of nontreated patients, proving that intravenously administered rhEPO reaches the brain. in the efficacy trial, patients received rhEPO within 5 hr of onset of symptoms (median, range 2:40-7:55). Admission neurologic scores and serum S100beta concentrations were strong predictors of outcome. Analysis of covariance controlled for these two variables indicated that rhEPO treatment was associated with an improvement in follow-up and outcome scales. A strong trend for reduction in infarct size in rhEPO patients as compared to controls was observed by MRI. Conclusion: intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month. A larger scale clinical trial is warranted.
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Molecular Medicine 
Institut für Allgemeinmedizin