Erythropoietin Epoetin

FigurG 5.3. Glycosylated erythropoietin (epoetin) with an N-linked glycosyl group and terminal sialic acid cap.

A. General description Erythropoietin is a glycoprotein normally produced in the kidneys and is responsible for the stimulation of red blood cell production. Epoetin alfa is derived via recombinant DNA techniques by mammalian cells after the insertion of the human erythropoietin gene its amino-acid sequence is identical to that of endogenous erythropoietin. Epoetin alfa... 

Erythropoietin, epoetin alfa, epoetin beta, epoetin gamma, and darbepoetin... 

Of the known hematopoietic growth factors, erythropoietin (epoetin alfa), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 11 are currently in clinical use. Thrombopoietin is undergoing clinical trials and will probably become available soon. Other potentially useful hematopoietic factors are still in development. 

Erythropoietin (Epoetin, EPO) had a global market of US 11.1 billion in 2004 (Research and Markets, 2005b) and was the top-selling biopharmaceutical worldwide. The patent on this biopharmaceutical, owned by the company Amgen, expired in 2004, paving the way for new companies to enter the market. 

Blood corpuscles develop from stem cells through several cell divisions (n = 17 ). Hemoglobin is then synthesized and the cell nucleus is extruded. Erythropoiesis is stimulated by the hormone erythropoietin (a glycoprotein), which is released from the kidneys when renal oxygen tension declines. A nephrogenic anemia can be ameliorated by parenteral administration of recombinant erythropoietin (epoetin alfa) or hyperglyco-sylated erythropoietin (darbepoetin longer half-life than epoetin). 

Recombinant human erythropoietin (epoetin and darbepoetin) provides effective therapy with a very favorable risk-benefit ratio in hemodialysis patients with end-stage chronic renal insufficiency, and in patients with progressive renal insufficiency who are not yet being dialysed (1). It improves cognitive function and the quality of life of patients with chronic uremia (2-5) and is very effective in children with chronic renal graft rejection and anemia (6). It also offers new opportunities for treating anemia in non-uremic patients. In patients with chemotherapy-induced anemia, epoetin increases hemoglobin concentration, reduces transfusion requirements, and improves quality of life (7,8). The response rate to epoetin in patients with multiple myeloma and anemia, which is 55-85% (9), increases when GM-CSF or G-CSF is... 

Podesta A, Carmagnini E, Parodi E, Dottori V, Crivellari R, Barberis L, Audo A, Lijoi A, Passerone G. Elective coronary and valve surgery without blood transfusion in patients treated with recombinant human erythropoietin (epoetin-alpha). Minerva Cardioangiol 2000 48(ll) 341-7. 

The human gene for erythropoietin, a hormone produced in the kidney, was first cloned in the 1980s (Jacobs et al, 1985), and the recombinant form was developed soon after that (Flaherty etal, 1989). The recombinant alpha form of erythropoietin, epoetin, is now very widely used in the context of the anaemia associated with... 

Erythropoietin, Epoetin-Alfa (Epogen, Procrit), USA44, 1987... 

Recombinant human erythropoietin epoetin cdfa) is nearly identical to the endogenous hormone. The carbohydrate modification pattern of the recombinant form differs slightly from that of the native protein, but this difference apparently does not alter kinetics, potency, or immunoreac-tivity of the drug. However, modem assays can detect these differences, which is of significance for detecting athletes who use the recombinant product for blood doping. ... 

Recombinant DNA technology products aldesleukin (IL-2, used in renal cancer) erythropoietin (epoetin alfa, used in anemias) filgrastim (G-CSF, used in neutropenia) interferon alpha (used in hepatitis B and C and in cancer), interferon beta (used in multiple sclerosis) interferon gamma (used in chronic granulomatous disease) oprelvekin (IL-11, used in thrombocytopenia) thrombopoietin (used in thrombocytopenia) and sargramostim (GM-CSF, used in neutropenia). 

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