Combination of Tmprss6-ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia

Haematologica

Volumn 101, Issue 1, 2016, Pages e8-e11

  Casu, Carla ^a   Aghajan, Mariam ^b   Oikonomidou, Paraskevi Rea ^a   Guo, Shuling ^b   Monia, Brett P ^b   Rivella, Stefano ^a  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b ISIS PHARMACEUTICALS   (United States)

Author keywords

Chelator; Erythropoiesis; Iron metabolism; Iron overload; Red blood cells

Indexed keywords

DEFERIPRONE; HEMOGLOBIN BETA CHAIN; HEPCIDIN; TRANSFERRIN; IRON CHELATING AGENT; MATRIPTASE 2; MEMBRANE PROTEIN; PYRIDONE DERIVATIVE; SERINE PROTEINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; BETA THALASSEMIA; ERYTHROPOIESIS; GENE MUTATION; HOMEOSTASIS; IRON OVERLOAD; LETTER; MOUSE; NONHUMAN; ANIMAL; ANTAGONISTS AND INHIBITORS; BETA-THALASSEMIA; DISEASE MODEL; DRUG EFFECTS; GENETICS; METABOLISM;

ANIMALS; BETA-THALASSEMIA; DISEASE MODELS, ANIMAL; ERYTHROPOIESIS; IRON CHELATING AGENTS; MEMBRANE PROTEINS; MICE; PYRIDONES; SERINE ENDOPEPTIDASES;

EID: 84952923690     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2015.133348     Document Type: Letter

References (12)

1. Ginzburg Y, Rivella S. beta-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood. 2011;118(16):4321-4330.
2. Rivella S. The role of ineffective erythropoiesis in non-transfusiondependent thalassemia. Blood Rev. 2012;26 Suppl 1:S12-15.
3. Rivella S. beta-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica. 2015;100(4):418-430.
4. Weizer-Stern O, Adamsky K, Amariglio N, et al. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera. Br J Haematol. 2006;135(1):129-138.
5. Weizer-Stern O, Adamsky K, Amariglio N, et al. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models. Am J Hematol. 2006;81(7):479-483.
6. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007;109(11):5027-5035.
7. Parrow NL, Gardenghi S, Ramos P, et al. Decreased hepcidin expression in murine beta-thalassemia is associated with suppression of Bmp/Smad signaling. Blood. 2012;119(13):3187-3189.
8. Schmidt PJ, Toudjarska I, Sendamarai AK, et al. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine beta-thalassemia intermedia. Blood. 2013;121(7):1200-1208.
9. Guo S, Casu C, Gardenghi S, et al. Reducing TMPRSS6 ameliorates hemochromatosis and beta-thalassemia in mice. J Clin Invest. 2013;123(4):1531-1541.
10. Schmidt PJ, Racie T, Westerman M, Fitzgerald K, Butler JS, Fleming MD. Combination therapy with a Tmprss6 RNAi-therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of beta-thalassemia intermedia. Am J Hematol. 2015;90(4):310-313.
11. Sohn YS, Breuer W, Munnich A, Cabantchik ZI. Redistribution of accumulated cell iron: a modality of chelation with therapeutic implications. Blood. 2008;111(3):1690-1699.
12. Libani IV, Guy EC, Melchiori L, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood. 2008;112(3):875-885.