The study authors conclude that advances in medical management and hematopoietic stem cell transplantation have improved and extended the lives of β-thalassemia patients significantly, however, new therapies are still required to further optimize care. Their findings suggest two novel therapeutic strategies to treat β-thalassemia by enhancing ULK1-mediated autophagy of free α-globin: pharmacological inhibition of mTORC1 or suppression of miR-451 by antagomirs.

The study authors conclude that in this analysis, 88% of treated evaluable patients in HGB-207 and HGB-212 achieved TI and demonstrated stable HbAT87Q and the safety profile was consistent with that of busulfan-based myeloablative conditioning. The authors also note, that Beti-cel–related events were consistent with side effects of DMSO, a cryoprotectant used in the drug product.

The study authors conclude that these results demonstrate that PKR activation with mitapivat was well tolerated and improved anemia, hemolysis, and ineffective erythropoiesis, and may represent a novel therapeutic approach for pts with α- or β-thalassemia.

The study authors conclude that their findings uncover an underexplored role of FGF-23 in bone and BM niche defects in BT, as a condition of severe anemia and chronic EPO stimulation, thus proposing FGF-23 as the molecule at the crossroads of erythropoiesis and bone metabolism. They demonstrate that the inhibition of FGF-23 signaling might provide a novel strategy to ameliorate bone compartment and restore HSC-BM niche interactions in BT, with potential translational relevance in improving HSC transplantation and gene therapy/editing approaches.