Non-erythropoietic tissue-protective peptides derived from erythropoietin: WO2009094172.

Erythropoietin (EPO) is a cytokine with erythropoietic and tissue protective activities. Its action as a tissue protective agent requires, however, high dosage that results in limiting side effects associated with abnormally augmented erythropoiesis. Elimination of the erythropoietic activity of EPO while preserving its tissue protective properties was nevertheless achieved in carbamoylated EPO (CEPO), whose therapeutic activity and apparent safety were documented in experimental models of nervous, heart, kidney and other tissue damage, justifying ongoing clinical trials. Here, we review patent application WO2009094172 by Araim Pharmaceuticals, which describes novel EPO-derived peptides having tissue protective but no erythropoietic activity. The preferred peptide, UEQLERALNSS, which mimics the external 3D structure of the helix B of EPO, was shown to exhibit the same spectrum of tissue protective activity as CEPO in several in vivo models. In addition, it could reduce radiation-induced mortality when administered 24 h after irradiation in mice, suggesting its possible utility in emergency situations after mass irradiation casualties. Owing to their low manufacturing cost, high stability and low immunogenicity, such peptides might well offer a superior alternative to CEPO for therapeutic tissue protection in human pathologies and are likely to provide valuable probes to study the molecular mechanisms of EPO-mediated cytoprotection.