Modern therapeutic approaches for β-thalassemia: from blood transfusion to gene therapy

Beta-thalassemia is a hereditary disorder caused by pathogenic variants in the HBB gene that lead to impaired synthesis of β-globin chains, resulting in ineffective erythropoiesis, development of microcytic hypochromic anemia, and a complex of systemic complications. This article reviews current therapeutic strategies for this condition. Adequate transfusion support combined with regular chelation therapy remains the cornerstone of standard treatment. In current practice, other methods of conservative therapy are also used, such as those targeting fetal hemoglobin induction, stimulation of erythropoiesis, and other pathogenetic mechanisms. Allogeneic hematopoietic stem cell transplantation was until recently the only method capable of providing a complete cure for β-thalassemia. However, its application is limited by the availability of a fully compatible donor and the risks of transplantation complications, including a high risk of graft failure in this disease and graft-versushost disease. The development of gene therapy aimed at restoring β-globin synthesis or inducing fetal hemoglobin expression offers prospects for functional cure without the need for allogeneic hematopoietic stem cell transplantation, overcoming many of its limitations, including the lack of an optimal donor, graft-versus-host disease, and graft rejection. This review provides an analysis of existing treatment methods, their limitations, and the potential for clinical application of gene therapy in β-thalassemia.

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