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Nephrol Dial Transplant (2002) 17: 8-12
© 2002 European Renal Association-European Dialysis and Transplant Association


Neuroprotective properties of epoetin alfa

Anthony Cerami1,, Michael Brines1, Pietro Ghezzi1,2, Carla Cerami1 and Loretta M. Itri3

1 The Kenneth S. Warren Institute, New York, USA, 2 Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy and 3 Genta, Inc., Berkeley Heights, New Jersey, USA

Abstract

Erythropoietin and its receptor function as primary mediators of the normal physiological response to hypoxia. Erythropoietin is recognized for its central role in erythropoiesis, but studies in which recombinant human erythropoietin (epoetin alfa) is injected directly into ischaemic rodent brain show that erythropoietin also mediates neuroprotection. Abundant expression of the erythropoietin receptor has been observed at brain capillaries, which could provide a route for circulating erythropoietin to enter the brain. In confirmation of this hypothesis, systemic administration of epoetin alfa before or up to 6 h after focal brain ischaemia reduced injury by 50–75%. Epoetin alfa also limited the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis and excitotoxicity induced by kainate. Thus, systemically administered epoetin alfa in animal models has neuroprotective effects, demonstrating its potential use after brain injury, trauma and multiple sclerosis. It is evident that erythropoietin has biological activities in addition to increasing red cell mass. Given the excellent safety profile of epoetin alfa, clinical trials evaluating systemically administered epoetin alfa as a general neuroprotective treatment are warranted.

Keywords: brain injury; encephalitis; epoetin alfa; erythropoietin; ischaemia; neuroprotection

Notes

Correspondence and offprint requests to: Anthony Cerami, The Kenneth S. Warren Institute, 712 Kitchawan Road, Ossining, NY 10562, USA. Tel: +1 914 762 7668, fax: +1 914 762 7445, e-mail: acerami{at}kswl.org


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