Transcript Clostridium difficile - University of California, Irvine

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.