Lysine-specific demethylase 1 is a therapeutic target for fetal hemoglobin induction

Enhanced fetal gamma-globin synthesis alleviates symptoms of beta-globinopathies such as sickle cell disease and beta-thalassemia, but current gamma-globin-inducing drugs offer limited beneficial effects. We show here that lysine-specific demethylase 1 (LSD1) inhibition by RNAi in human erythroid cells or by the monoamine oxidase inhibitor tranylcypromine in human erythroid cells or beta-type globin-transgenic mice enhances gamma-globin expression. LSD1 is thus a promising therapeutic target for gamma-globin induction, and tranylcypromine may serve as a lead compound for the development of a new gamma-globin inducer.