title: Advances in experimental treatment of beta-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.
authors.affiliation: Molecular and Clinical Hematology Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892, USA. gprod@helix.nih.gov
authors.forename: G P
authors.initials: GP
authors.lastname: Rodgers
authors.forename: Y
authors.initials: Y
authors.lastname: Saunthararajah
mesh_terms: D001374:Azacitidine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007502:Iron Chelating Agents / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000188:drug therapy*
chemical_list: D056572:Histone Deacetylase Inhibitors; D007502:Iron Chelating Agents; D004921:Erythropoietin; D001374:Azacitidine; D006918:Hydroxyurea