Treatment of erythropoietin deficiency in mice with systemically administered siRNA

W Querbes, RL Bogorad, J Moslehi… - Blood, The Journal …, 2012 - ashpublications.org
W Querbes, RL Bogorad, J Moslehi, J Wong, AY Chan, E Bulgakova, S Kuchimanchi…
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
Anemia linked to a relative deficiency of renal erythropoietin production is a significant
cause of morbidity and medical expenditures in the developed world. Recombinant
erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover,
some patients become refractory to erythropoietin because of increased production of
factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major
source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic …
Abstract
Anemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic erythropoietin production and suppress hepcidin levels using systemically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading to improved RBC production in models of anemia caused by either renal insufficiency or chronic inflammation with enhanced hepcidin production.
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