Changing the scene on thalassemias
LINKS TO ABSTRACTS:
Presentation ID p433-1
Christophe Lechauve, United States
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.
Presentation ID p433-2
Franco Locatelli, Rome, Italy
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.
Presentation ID p433-3
Kevin Kuo, Toronto, Canada
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.
Presentation ID p433-4
Annamaria Aprile, Italy
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.
Presentation ID p433-5
Presenter: Maria Rosa Lidonnici, Milan, Italy
The study authors conclude that their findings show that Bthal HSCs are exiting from the quiescent state towards a preferential erythroid differentiation. They demonstrate that the drivers are likely specific niche signals, linked to the TGFß, and chronic BM stimulation or, alternatively, a specific regulation of the ‘erythroid branching’, naturally present in the HSC pool, which is exacerbated by the pathophysiology of the disease.