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          Institute: MPI für experimentelle Medizin     Collection: Clinical Neuroscience     Display Documents



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ID: 18550.0, MPI für experimentelle Medizin / Clinical Neuroscience
Erythropoietin therapy for acute stroke is both safe and beneficial
Authors:Ehrenreich, Hannelore; Hasselblatt, M.; Dembowski, C.; Cepek, L.; Lewczuk, P.; Stiefel, M.; Rustenbeck, H. H.; Breiter, N.; Jacob, S.; Knerlich, F.; Bohn, M.; Poser, W.; Rüther, E.; Kochen, M.; Gefeller, O.; Gleiter, C.; Wessel, T. C.; De Ryck, M.; Itri, L.; Prange, H.; Cerami, A.; Brines, M.; Sirén, Anna Leena
Language:English
Date of Publication (YYYY-MM-DD):2002-08
Title of Journal:Molecular Medicine
Journal Abbrev.:Mol. Med.
Volume:8
Issue / Number:8
Start Page:495
End Page:505
Review Status:Peer-review
Audience:Experts Only
Abstract / Description: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 <80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset <8 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.
External Publication Status:published
Document Type:Article
Communicated by:Hannelore Ehrenreich
Affiliations:MPI für experimentelle Medizin/Clinical neuroscience
External Affiliations:Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany; Univ Gottingen, Dept Psychiat, D-37075 Gottingen, Germany; Univ Gottingen, Dept Radiol 1, D-37075 Gottingen, Germany; Univ Gottingen, Dept Radiol 3, D-37075 Gottingen, Germany; Univ Gottingen, Clin Pharm, D-37075 Gottingen, Germany; Univ Gottingen, Dept Family Med, D-37075 Gottingen, Germany; Univ Erlangen Nurnberg, Dept Med Stat, Erlangen, Germany; Univ Tubingen, Dept Clin Pharmacol, Tubingen, Germany; Janssen Res Fdn, Titusville, NJ USA; Janssen Res Fdn, Dept Neuropharmacol, B-2340 Beerse, Belgium; Ortho Biotech Inc, Raritan, NJ USA; Kenneth S Warren Inst, Kitchawan, NY USA
Identifiers:ISI:000178684900008 [ID No:1]
ISSN:1076-1551 [ID No:2]
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