Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice

Hydroxyurea with AKT2 inhibition decreases vaso-occlusive events in sickle cell disease mice

Barazia A, (2015), Blood (Link to Abstract)              


Hydroxyurea (HU) is the established mainstay of chronic treatment in sickle cell disease (SCD). HU was shown to stimulate HbF production, serve as an NO donor, and inhibit tissue factor expression in leukocytes. HU was also effective as acute vaso-occlusive crisis (VOC) treatment in SCD mouse models. The authors of this manuscript showed that co-administration of hydroxyurea and Akti XII, an AKT2 inhibitor, did have beneficial effect and prolonged survival in SCD mice with VOC. AKT2 plays an important role in neutrophil-erythrocyte and neutrophil-platelet interaction and its inhibition led to increased blood flow in affected areas of VOC.


* AKT2 inhibition might be a novel target in the acute VOC of SCD patients improving perfusion of affected tissues.