Novel therapies in Beta-thalassaemia.

Beta-thalassaemia is one of the most significant haemoglobinopathies worldwide resulting in the synthesis of little or no β-globin chains. Without treatment, β-thalassaemia major is lethal within the first decade of life due to the complex pathophysiology which leads to wide clinical manifestations. Current clinical management for these patients depends on repeated transfusions followed by iron chelating therapy. A number of novel approaches to correct the resulting α/β globin chain imbalance, treat ineffective erythropoiesis and improve iron overload are currently being developed. Up to now, the only curative treatment for beta-thalassemia is HSCT, but this is a risky and costly procedure. Gene therapy, gene editing and base editing are emerging as a powerful approach to treat this disease. In β-thalassaemia, gene therapy involves the insertion of a vector containing the normal β-globin or γ-globin gene into hematopoietic stem cells to permanently produce normal red blood cells. Gene editing and base editing involves the use of ZFNs, TALENs and CRISPR/Cas9 to either correct the causative mutation or else insert a mutation that will increase foetal haemoglobin. In this review we will mention the current management strategies used to treat beta-thalassaemia and focus on the novel therapies. In this review we will mention the current management strategies used to treat beta-thalassaemia and focus on the novel therapies targeting ineffective erythropoiesis, improving iron overload and correction of the globin chain imbalance.