Future alternative therapies for β-thalassemia

Abstract

β-thalassemia is an inherited disorder due to mutations found in the β-globin gene, leading to anemia and requiring sporadic or chronic blood transfusions for survival. Without proper chelation, β-thalassemia results in iron overload. Ineffective erythropoiesis can lead to iron overload even in untransfused patients who are affected by β-thalassemia intermedia. Better understanding of the molecular biologic aspects of this disorder has led to improvements in population screening and prenatal diagnosis, which, in turn, have led to dramatic reductions in the number of children born with β-thalassemia major in the Mediterranean littoral. However, as a consequence of decreases in neonatal and childhood mortality in other geographical areas, β-thalassemia has become a worldwide clinical problem. A number of unsolved pathophysiological issues remain, such as ineffective erythropoieis, abnormal iron absorption, oxidative stress, splenomegaly and thrombosis. In the last few years, novel studies have the potential to introduce new therapeutic approaches that might reduce these problems and limit the need for blood transfusion.

Keywords::

• anemia
• β-thalassemia
• erythropoietin
• ferroportin
• fetal hemoglobin
• gene transfer
• hepcidin
• ineffective erythropoiesis
• iron metabolism
• Jak2
• lentiviral vector
• radicals
• reactive oxygen species

Financial & competing interests disclosure

This work was funded by the Carlo and Micol Schejola Foundation, NIH-NIDDK and the Cooley’s Anemia Foundation 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.