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Erythropoietin

Erythropoietin. Justin Tuwatananurak T-RAP Fall 2011. Background Info. First identified in the early 1900s when Paul Carnot observed that rabbits subject to hemotropic factor hemopoeitin (later renamed erythropoietin) exhibited increased RBC production.

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Erythropoietin

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  1. Erythropoietin Justin Tuwatananurak T-RAP Fall 2011

  2. Background Info • First identified in the early 1900s when Paul Carnot observed that rabbits subject to hemotropic factor hemopoeitin (later renamed erythropoietin) exhibited increased RBC production. • Peptide hormone (glycoprotein); functions as a cytokine for RBC precursors located in bone marrow. • Was first synthesized in 1985 at Columbia University, and a synthetic from of erythropoietin (Epo) was approved by the FDA in 1989.

  3. Function • Primary effect: Increase hematocrit, or % of RBCs in blood. • Cooperates with growth factors (SCIF, GM-CSF, 1L-3, and IGF-1) to stimulate RBC production. • Prevent erythrocytes from undergoing apoptosis. • Also can promote angiogenesis, increase blood pressure, and induce smooth muscle proliferation. • Increase iron absorption by suppressing hepcidin.

  4. Regulation

  5. Medical applications • Generally used to treat patients with anemia. • Chronic kidney disease • Myelodysplasia resulting from cancer treatment • Administered via injections or IV drip • Compatible with Jehovah’s Witness religious doctrine, since it’s not a blood transfusion.

  6. Blood Doping • Epo can be used to improve athletic endurance by increasing RBC count, allowing for higher blood oxygenation and O2 transport to the muscles. • Has been banned since the early 1990’s as a PED. • Can test for blood doping by checking the urine for recombinant Epo, but detection is still difficult.

  7. Potential side effects • Increased hematocrit may lead to blood thickening • Thrombosis • Stroke • Hypertension • Various Drug Interactions • Lenalidomide: increased risk of thrombosis • Cyclosporine: additive effects on increasing blood pressure • Increased risk of tumor growth in chemo patients

  8. Recent developments • 2007: FDA strengthens safety information for erythropoesis-stimulating agents • Recommends using smallest possible dose to avoid blood tranfusions, and to monitor hemoglobin levels • Affymax, Inc. developing peginesatide, a once-monthly erythropoiesis-stimulating agent. • Fibrogen currently developing HIF-PHIs, which are taken orally to stimulate endogenous Epo production.

  9. References • FDA • http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108864.htm • MarketWatch • http://www.marketwatch.com/story/affymaxr-receives-10-million-milestone-payment-for-fda-filing-of-new-drug-application-for-hematidetmpeginesatide-2011-08-10?reflink=MW_news_stmp • PubMed: Epoetin Alpha Injection • http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000913/ • Fibrogen: HIF-PHI therapy • http://www.fibrogen.com/HIF_PHI_Therapy • R. Niesvizky, A. Spencer, M. Wang, D. Weber, C. Chen, M. A. Dimopoulos, Z. Yu, Z. Yu, R. Delap, J. Zeldis, R. D. Knight. Increased risk of thrombosis with lenalidomide in combination with dexamethasone and erythropoeitin. Journal of Clinical Oncology (2006) 24(18): 7506.

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