Work

Combination therapy with a T mprss6 RNA i‐therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of β‐thalassemia intermedia

Year: 2015

Type: article

Abstract: β-thalassemias result from diminished β-globin synthesis and are associated with ineffective erythropoiesis and secondary iron overload caused by inappropriately low levels of the iron regulatory hormone hepcidin. The serine protease TMPRSS6 attenuates hepcidin production in response to iron stores. Hepcidin induction reduces iron overload and mitigates anemia in murine models of β-thalassemia intermedia. To further interrogate the efficacy of an RNAi-therapeutic downregulating Tmprss6, β-thalassemic Hbb(th3/+) animals on an iron replete, an iron deficient, or an iron replete diet also containing the iron chelator deferiprone were treated with Tmprss6 siRNA. We demonstrate that the total body iron burden is markedly improved in Hbb(th3/+) animals treated with siRNA and chelated with oral deferiprone, representing a significant improvement compared to either compound alone. These data indicate that siRNA suppression of Tmprss6, in conjunction with oral iron chelation therapy, may prove superior for treatment of anemia and secondary iron loading seen in β-thalassemia intermedia.

Source: American Journal of Hematology

DOI: 10.1002/ajh.23934

Authors: Paul J. Schmidt, Tim Racie, Mark Westerman, Kevin Fitzgerald, James S. Butler, Mark D. Fleming

Institutions: Boston Children's Hospital, Harvard University, Alnylam Pharmaceuticals (United States), Intrinsic LifeSciences (United States)

Language: English

Topic: Iron Metabolism and Disorders

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,450