Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach

Abstract

Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.

Keywords: Erythropoiesis-stimulating agents; Erythropoietin; Human recombinant erythropoietin.

Fig. 1

Biological structure of EPO. Erythropoietin has two intramolecular di-sulfide bonds at positions Cys7–Cys161 and Cys29–Cys33. Moreover, the N-glycosylated bonds at the asparagine 24, 38, and 83 residues and an O-glycosidic bond is located at amino acid position 126