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CAN ERYTHROPOIETIN AND MIMETICS BE USED AS NOVEL NEUROPROTECTIVE AGENTS?

Abstract

Erythropoietin (EPO) is a glycopeptide hormone produced in the kidney in response to hypoxia. It is known for its role in red blood cell formation but has also, in recent years, been found in other locations like the central nervous system where its receptors are specifically expressed, suggesting an endogenous role in this location. EPO and its mimetics hold promise for clinical use in neuroprotection. As in studies of previous neuroprotective agents, in vitro and in vivo animal models have found that EPO has important neuroprotective actions in stroke, ischaemia and other neurological injury, mediated by inhibition of apoptosis and induction of angiogenesis. Although a randomised trial of 40 stroke patients found a non-significant neurological improvement with EPO, there are no large trials of EPO neuroprotection. Therefore the benefits of EPO recorded in animal models have not yet been replicated in human populations.
Larger trials of EPO in stroke and other neurological disease patients will need to be embarked upon. Practical issues like drug dosing, randomisation and point in therapeutic window at which intervention is received will need to be reviewed.

EPO and its mimetics hold an impressive promise for potential clinical use in neuroprotection. As in studies of previous neuroprotective agents, in vitro and in vivo animal models have found that EPO has important neuroprotective actions in stroke, ischaemia and other neurological injury, mediated by inhibition of apoptosis and induction of angiogenesis. Although a small randomised trial of stroke patients found a non-significant neurological improvement with high dose EPO, there are no large trials of EPO neuroprotection. Therefore the benefits of EPO recorded in animal models have not yet been replicated in human populations. The likelihood of this happening in the near future will be determined by a number of factors, favourable and unfavourable. Larger trials of EPO in stroke and other neurological disease patients will need to be embarked upon. Practical issues like drug dosing, randomisation and point in therapeutic window at which intervention is received will need to be reviewed.

These do not however take away from the fact that EPO is a promising weapon in the armament against neurological injury and will someday, along with its mimetics, prove useful novel neuroprotective agents.

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