Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies

Abstract

Fetal globin (gamma globin; HBG) is normally expressed during fetal life and prevents the clinical manifestations of beta hemoglobinopathies before birth. HBG genes are normally integrated in hematopoietic stem cells in all humans, and are at least partially amenable to reactivation. Inducing expression of fetal globin (HBG) gene expression to 60% to 70% of alpha globin synthesis produces a β-thalassemia trait phenotype, and reduces anemia. Tailoring combinations of therapeutics to patient subsets characterized for quantitative trait loci which modulate basal fetal hemoglobin and erythroid cell survival should provide effective amelioration of clinical symptoms in β-thalassemia and sickle cell disease.

Keywords: Beta-thalassemia; Fetal hemoglobin; Genetic modifiers; Sickle cell disease; Stress signaling.