Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

Rayan Bou-Fakhredin, Lucia De Franceschi, Irene Motta, Maria Domenica Cappellini, Ali T Taher, Rayan Bou-Fakhredin, Lucia De Franceschi, Irene Motta, Maria Domenica Cappellini, Ali T Taher

Abstract

A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.

Keywords: fetal hemoglobin; globin gene; pharmacological induction; sickle cell disease; β-thalassemia; γ-globin.

Conflict of interest statement

R.B.-F. has nothing to disclose. L.D.F. serves on the advisory board of Novartis, Roche and Vifor. I.M. reports receiving honoraria from Sanofi-Genzyme and Amicus Therapeutics and serves on the advisory boards for Bristol Myers Squibb/Celgene. M.D.C. serves on the advisory boards for Bristol Myers Squibb/Celgene, Sanofi/Genzyme, Agios, Silence Therapeutics, Vertex and Vifor. A.T.T. reports receiving consultancy from Novartis, Bristol Myers Squibb/Celgene, Vifor Pharma, Ionis Pharmaceuticals, Imara and Agios Pharmaceuticals, and research funding from Novartis, Bristol Myers Squibb, Vifor Pharma, Imara and Ionis Pharmaceuticals.

Figures

Figure 1
Figure 1
Summary of all established pharmacological approaches and experimental therapeutic strategies for HbF induction in β-thalassemia and SCD.

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