Derivatives of erythropoitein that are tissue protective but not erythropoietic

Marcel Leis, Pietro Gliezzi, Giovanni Grasso, Roberto Bianchi, Pia Vilia, Maddalena Fratelli, Costanza Savino, Marina Bianchi, Jacob Nielsen, Jens Gerwien, Pekka Kallunki, Anna Kirstine Larsen, Lone Helboe, Søren Christensen, Lars O. Pedersen, Mette Nielsen, Lars Torup, Thomas Sager, Alessandra Sfacteria, Serhat ErbayraktarZubeyde Erbayraktar, Necati Gokmen, Osman Yilmaz, Carla Cerami-Hand, Qiao Wen Xie, Thomas Coleman, Anthony Cerami, Michael Brines

Research output: Contribution to journalArticlepeer-review

Abstract

Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.

Original languageEnglish
Pages (from-to)239-242
Number of pages4
JournalScience
Volume305
Issue number5681
DOIs
Publication statusPublished - Jul 9 2004

ASJC Scopus subject areas

  • General

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