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

Shi, Lihong; Cui, Shuaiying; Engel, James D; Tanabe, Osamu · Nat Med · 2013

basic_science · Level V

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Abstract

Enhanced fetal γ-globin synthesis alleviates symptoms of β-globinopathies such as sickle cell disease and β-thalassemia, but current γ-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 β-type globin-transgenic mice enhances γ-globin expression. LSD1 is thus a promising therapeutic target for γ-globin induction, and tranylcypromine may serve as a lead compound for the development of a new γ-globin inducer.

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