Startseite Kongressberichte 2020 Virtual Edition of the 25th Annual Congress of the European Hematology Association Oral Sessions Red & White Cell Disorders Iron in focus
 
Oriana Marques, Natalie Horvat, Richard Sparla, et al.
 
The authors of the abstract conclude: 
These results significantly extend our knowledge of FPN regulation in response to inflammation and explain mechanisms underlying the pathophysiology of Anemia of Inflammation as well as their potential for counteracting these disease mechanisms for the treatment of Anemia of Inflammation.  
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Violante Olivari, Mariam Aghajan, Maria Rosa Lidonnici, et al.
 
The authors of the abstract conclude: 
Overall our findings prove that Tfr2 targeting may be a novel “erythropoiesis-stimulating” approach for anemia of CKD, but Tfr2 inhibition should be tightly controlled. Indeed, we propose that the initial beneficial effect of TFR2-ASOs, likely due to an early erythroid Tfr2 inhibition, is lost over time for the iron toxicity due to excessive hepatic Tfr2 downregulation. We are working to identify the optimal treatment protocol to balance Tfr2 downregulation in erythroid cells and in the liver, to adjust iron supply according to the enhanced erythropoiesis.
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Mariateresa Pettinato, Mariam Aghajan, Alessandro Dulja, et al.
 
The authors of the abstract conclude: 

- Fkbp12 downregulation in the spleen increases immature erythropoiesis and upregulates the hepcidin inhibitor Erfe, likely contrasting the ASO activating effect and revealing a new role of FKBP12 in erythropoiesis; the latter is relevant considering that FKBP12 is sequestered by immunosuppressive drugs, commonly used in clinics

- Fkbp12 downregulation increases Tmprss6 expression, whereas the combined targeting of the two inhibitors by ASOs synergistically increases hepcidin expression even when with partial Tmprss6inhibition.

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Thomas Backus, Natalia Medeiros, Evan Lema, et al.
 
The authors of the abstract conclude: 
KTI-2338 is efficacious at increasing serum iron levels at doses as low as 0.5mg/kg, which persist for up to 16hrs in wild-type mice.  A novel murine model of IRIDA phenocopies changes in hepcidin and serum iron observed in IRIDA patients and treatment with the selective ALK2 inhibitor KTI-2338 decreased serum hepcidin and increased serum iron in this model. These data demonstrate ALK2 inhibition has potential to improve iron levels and anemia in IRIDA patients. Further, ALK2 modulation of hepcidin represents a promising therapeutic for other hepcidin mediated anemias such as chronic kidney disease or anemia of inflammation. 
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Heinrich Lob, Leah Kravets, Jenny Yang, et al.
 
The authors of the abstract conclude: 
Our data suggest that liver iron loading significantly alters glucose metabolism. Potential mechanisms involve increased gluconeogenesis and blunted glycolysis. Both lead to chronic elevations of basal blood glucose, which exhausts insulin production and ultimately contributing to T2D.