Neuroprotection with or without erythropoiesis; sometimes less is more.
Erythropoietin (EPO) is a pleiotropic cytokine with a therapeutic potential that goes well beyond the treatment of anaemia. The study by Wang et al (2007b) examined the protective effects of EPO in a rat model of embolic stroke. The efficacy and haematological side effects of EPO were compared to those of a carbamylated EPO variant (CEPO). Treatment with EPO dose-dependently reduced infarct volume and improved long-term functional outcome. However, an increase in hematocrit was seen even for doses of EPO that did not offer neuroprotection. These data do not suggest the existence of a therapeutic window between effect and side effect for treatment with EPO. Treatment with CEPO was without haematological side effects.
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Section of Neuropharmacology, Division of Disease Pharmacology, H Lundbeck A/S, Ottiliavej 9, 2500 Copenhagen, Denmark. LTO@lundbeck.com
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006400:Hematocrit; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy*
D018696:Neuroprotective Agents; C488171:carbamylated erythropoietin; D004921:Erythropoietin