Combining gene therapy and fetal hemoglobin induction for treatment of β-thalassemia

Abstract

β-thalassemias are caused by nearly 300 mutations of the β-globin gene, leading to a low or absent production of adult hemoglobin (HbA). Two major therapeutic approaches have recently been proposed: gene therapy and induction of fetal hemoglobin (HbF) with the objective of achieving clinically relevant levels of Hbs. The objective of this article is to describe the development of therapeutic strategies based on a combination of gene therapy and induction of HbFs. An increase of β-globin gene expression in β-thalassemia cells can be achieved by gene therapy, although de novo production of clinically relevant levels of adult Hb may be difficult to obtain. On the other hand, an increased production of HbF is beneficial in β-thalassemia. The combination of gene therapy and HbF induction appears to be a pertinent strategy to achieve clinically relevant results.

Keywords::

• β-thalassemia
• erythroid progenitor cells
• gene therapy
• hemoglobin
• high persistency of fetal hemoglobin
• sickle cell anemia

Acknowledgments

The authors would like to thank the Associazione Veneta per la Lotta Contro la Thalassemia, the Thalassaemia Modular Stratification System for personalized therapy of β-thalassemia and the THELETHON grant #GG10214.

Financial & competing interests disclosure

S Rivella is a consultant for Novartis, Bayer, Biomarin, Merganser, Imago and Isis Pharmaceuticals, owns equity of Merganser Pharmaceuticals, is a co-inventor for the patents US8058061 B2 C12 20111115 and US7541179 B2 C12N 20090602, and is supported by the NIH grant RO1 HL102449-03. The consulting work and intellectual property of S Rivella did not affect in any way the design, conduct or reporting of the research described in this manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.