Clostridium difficile - University of California, Irvine
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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.
• 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.
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.
Regulation
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.
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.
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
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.
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-fdafiling-of-new-drug-application-for-hematidetmpeginesatide-2011-0810?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.