Effect of voxelotor on murine bone marrow and peripheral blood with hematopoietic progenitor cell mobilization for gene therapy of sickle cell disease

Abstract

In preparation for hematopoietic stem cell mobilization and collection, current ex vivo gene therapy protocols for sickle cell disease require patients to undergo several months of chronic red cell transfusion. For health care equity, alternatives to red cell transfusion should be available. We examined whether treatment with GBT1118, the murine analog of voxelotor, could be a safe and feasible alternative to red cell transfusion. We found that 3 weeks of treatment with GBT1118 increased the percentage of bone marrow hematopoietic stem cells and upon plerixafor mobilization, the percentage of peripheral blood hematopoietic stem cells. Our data suggest that voxelotor should be further explored for its potential safety and utility as preparation for hematopoietic stem cell mobilization and collection.

Keywords: Bone marrow; Gene therapy; Hematopoietic stem cell mobilization; Hematopoietic stem cells; Plerixafor; Sickle cell disease; Voxelotor.