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

Abstract

Importance of the field: 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.

Areas covered in this review: This review covers translational and clinical studies carried out over the period 1998 – 2010.

What the reader will gain: 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.

Take home message: 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.

Keywords::

• acute ischemic stroke
• behavior
• carbamyl erythropoietin
• CEPO
• embolism
• mortality
• neuroprotection
• toxicity
• translational science

Notes

This box summarizes key points contained in the article.