부산대학교 도서관

β thalassemia (β thal) is a worldwide red blood cell (RBC) genetic disorder with limited therapeutic tools. Standard of care includes chronic RBC transfusions and iron chelation. In β thal, pathophysiologic studies have shown that oxidation plays a key role in both ineffective erythropoiesis and reduced survival of mature red cells in the peripheral circulation (Matte et al ARS 28: 1-14, 2018; Matte A et al. ARS 23: 1284, 2015). Recently, in a mouse model of β thal, we showed that the investigational pyruvate kinase (PK) activator mitapivat significantly improved anemia by targeting both ineffective erythropoiesis and hemolysis (Matte et al. JCI 131: e144206, 2021). We also found that mitapivat ameliorated the erythroid cell maturation index for in vitroCD34+ derived erythroblasts from β thal (cod b039) patients (Matte et al. JCI 131: e144206, 2021). The results of phase 2 proof-of-concept study (NCT03692052) in non-transfusion-dependent thalassemic patients support the beneficial effects of mitapivat on β thal (Kuo KHM et al Lancet 400: 493-501, 2022).