Combination of Tmprss6-ASO and the Iron Chelator Deferiprone Improves Erythropoiesis and Reduces Iron Overload in a Mouse Model of Beta-Thalassemia

TL;DRAbstract

Abstract Patients affected by non-transfusion dependent thalassemia (NTDT) do not require chronic blood transfusion for survival. However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis (IE), the hallmark of disease, leads to a variety of serious clinical morbidities. In NTDT the master regulator of iron homeostasis, hepcidin, is chronically repressed. Consequently, patients absorb abnormally high levels of iron, which eventually requires iron chelation to prevent the clinical sequelaes associated with iron overload. It has been shown that in mice affected by NTDT (Hbbth3/+), a second-generation antisense oligonucleotide (Tmprss6-ASO) can reduce expression of transmembrane serine protease Tmprss6, the major suppressor of hepcidin expression. This leads to reduction of hemichrome formation in erythroid cells, amelioration of IE and splenomegaly, and increased hemoglobin levels (Guo et al, JCI, 2013). Now we propose the use of Tmprss6-AS

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