Novel Erythropoietic Agents : A Threat to Sportsmanship / Wolfgang Ernst Bernard Jelkmann. - (Medicina Sportiva 11 (2007) 2; p. 32-42)
The mass of hemoglobin (Hb) is an important determinant of aerobic power. Red blood cell production is stimulated by
the glycoprotein erythropoietin (EPO). Recombinant human EPO (rHuEPO) engineered in Chinese hamster ovary (CHO)
cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected in urine by isoelectric focusing, because the pattern of their glycans differs from that of endogenous EPO. However, doping control is becoming much more difficult, as various novel erythropoiesis stimulating agents (ESAs) are - or are to come - on the market. Gene-activated EPO (Epoetin delta) from human fibrosarcoma cells (HT-1080) has been approved in the European Union. rHuEPO (Epoetin omega) produced in transformed baby hamster kidney (BHK) cells is also available. ESAs to come include Biosimilars of the established Epoetins, long-acting pegylated Epoetin beta (CERA), EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (Hematide) as well as non-peptidic EPO mimetics. Furthermore, small orally active drugs that are capable of stimulating endogenous EPO production are in preclinical or clinical trials. These include stabilizers of the hypoxia-inducible transcription factors (HIF) that bind to the EPO gene enhancer and GATA inhibitors which prevent GATA from suppressing the EPO gene promoter. It is crucial to inform the athletes and their supporting staff on the potential health risks.