Nonhematopoietic Variants of Erythropoietin in Ischemic Stroke: Need for Step-Wise Proof-of-Concept Studies

Dirk M Hermann

doi:10.1100/tsw.2010.226

Abstract

Neuroprotective, but not hematopoietic, variants of erythropoietin (EPO), such as Neuro-EPO, are promising candidates for treatment in the acute and subacute stroke phase. Characterized by its low sialic acid content and therefore exhibiting a very short plasma half-life, Neuro-EPO can probably not be administered systemically via the blood. As such, alternate routes of delivery are required. In their paper that now appears in TheScientificWorldJOURNAL, Rodríguez Cruz and colleagues provide evidence that Neuro-EPO promotes neurological recovery in the ischemic gerbil brain in a way that is similarly potent, if not superior, to systemically administered EPO. In view of the potential clinical use of Neuro-EPO, stringent proof-of-concept studies are urgently needed to define (1) how intranasally delivered Neuro-EPO reaches the brain, (2) which concentrations are achieved in the ischemic and nonischemic brain tissue of rodents and nonhuman primates, and (3) which are the mechanisms via which Neuro-EPO protects from injury. Only with such information should decisions be made whether intranasal Neuro-EPO may be evaluated in human patients.

Highlights

Based on its potent neuroprotective[1,2] and neuronal plasticity-promoting[3] actions, the hematopoietic growth factor erythropoietin (EPO) is an attractive candidate for stroke treatment
Experimental studies rapidly led to clinical trials in which the growth factor was administered to human patients with ischemic stroke
In their paper, which appears in parallel in TheScientificWorldJOURNAL, Rodríguez Cruz et al.[7] have shown that Neuro-EPO, which is characterized by its low sialic acid content, exhibits more potent neuroprotective effects in a gerbil model of brain ischemia when intranasally administered than conventional EPO that was systemically applied

Summary

Introduction

Based on its potent neuroprotective[1,2] and neuronal plasticity-promoting[3] actions, the hematopoietic growth factor erythropoietin (EPO) is an attractive candidate for stroke treatment. Experimental studies rapidly led to clinical trials in which the growth factor was administered to human patients with ischemic stroke.

Results

Conclusion