Tmprss6 ASO

"Tmprss6 ASO" is an antisense oligonucleotide (ASO) designed to inhibit the hepatic transmembrane serine protease Tmprss6. Tmprss6 functions as a negative regulator of hepatic hepcidin transcription by dampening iron-related BMP signaling in hepatocytes. The therapeutic goal of Tmprss6 ASO is to increase hepcidin levels, thereby reducing excessive iron absorption and mitigating iron overload, a significant cause of morbidity and mortality in beta-thalassemia. Preclinical studies in mouse models of thalassemia have demonstrated that Tmprss6 ASO treatment can decrease serum and liver iron, improve ineffective erythropoiesis, increase hemoglobin and red blood cell count, and reduce splenomegaly. However, its effectiveness has been observed to be blunted in conditions of severe iron overload, such as those caused by high erythroferrone concentrations or exogenous iron administration.