Erythropoietin molecules to treat acute ischemic stroke: a translational dilemma

• Published in: Expert opinion on investigational drugs Vol. 19; no. 10; p. 1179
• Main Author: Lapchak, Paul A
• Format: Journal Article
• Language: English
• Published: England 01.10.2010
• Subjects: Adult; Aged; Aged, 80 and over; Brain Ischemia - drug therapy; Clinical Trials as Topic; Drug Evaluation, Preclinical; Erythropoietin - adverse effects; Erythropoietin - analogs & derivatives; Erythropoietin - therapeutic use; Female; Humans; Male; Middle Aged; Signal Transduction; Stroke - drug therapy; Translational Medical Research; Young Adult
• ISSN: 1744-7658
• DOI: 10.1517/13543784.2010.517954

Since the realization that erythropoietin (EPO) molecules have 'neuroprotective' properties, they have been investigated as treatments for acute ischemic stroke (AIS), but not systematically. The results of the 2009 clinical trial showed that EPO was ineffective as a stroke treatment, and moreover, increased mortality when combined with tissue plasminogen activator. Currently, CEPO, an EPO analog, is entering into a safety, tolerability and pharmacokinetic clinical trial for the treatment of AIS. This review covers translational and clinical studies carried out over the period 1998 - 2010. The primary aim of this article is to review the information available regarding the pharmacological and biological characteristics of EPO molecules. Second, based upon the translational research with EPO molecules in preclinical stroke models, a recommendation is made regarding the continued development of EPO molecules as an option to treat AIS. EPO, CEPO and helix B peptide EPO analogs have significant neuroprotective activity is preclinical stroke models. However, given the detrimental effect of EPO in a recent clinical trial, preclinical safety studies of EPO molecules in embolic stroke models that parallel acute ischemic stroke in humans are warrented.