Erythropoietin molecules to treat acute ischemic stroke: a translational dilemma!
BACKGROUND
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.


METHODS
This review covers translational and clinical studies carried out over the period 1998 - 2010.


RESULTS
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.


CONCLUSIONS
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.
Lapchak
Paul A
PA
Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Paul.Lapchak@cshs.org
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy*; D057170:Translational Research, Biomedical; D055815:Young Adult
D004921:Erythropoietin