Advances in experimental treatment of β-thalassaemia

Abstract

Beta-thalassaemia is highly prevalent and world wide in its distribution. The gene to modify the clinical course of patients with transfusion-dependent thalassaemia (thalassaemia major), the gamma-globin gene, is already present in these patients but silenced in the course of development. During erythropoiesis, progenitors are believed to go through a phase where the milieu favours gamma-globin production. One pharmacological strategy to increase gamma-globin production is directed at recruiting such early progenitors through the use of cytotoxic agents (+/- erythropoietin) that presumably deplete more mature progenitors. Another promising strategy is to use chromatin-modifying agents that prevent the silencing of the gamma-globin gene that occurs during development. These agents, the methyl-transferase inhibitors and histone deacetylase inhibitors, either alone or in combination, may be able to produce the robust increase in gamma-globin and hence fetal haemoglobin and total haemoglobin, needed to successfully treat thalassaemia major. Studies of these agents, which are already available for clinical trials, should be encouraged.