Current and future alternative therapies for beta-thalassemia major

Abstract

Beta-thalassemia is a group of frequent genetic disorders resulting in the synthesis of little or no β-globin chains. Novel approaches are being developed to correct the resulting α/β-globin chain imbalance, in an effort to move beyond the palliative management of this disease and the complications of its treatment (e.g. life-long red blood cell transfusion, iron chelation, splenectomy), which impose high costs on healthcare systems. Three approaches are envisaged: fetal globin gene reactivation by pharmacological compounds injected into patients throughout their lives, allogeneic hematopoietic stem cell transplantation (HSCT), and gene therapy. HSCT is currently the only treatment shown to provide an effective, definitive cure for β-thalassemia. However, this procedure remains risky and histocompatible donors are identified for only a small fraction of patients. New pharmacological compounds are being tested, but none has yet made it into common clinical practice for the treatment of beta-thalassemia major. Gene therapy is in the experimental phase. It is emerging as a powerful approach without the immunological complications of HSCT, but with other possible drawbacks. Rapid progress is being made in this field, and long-term efficacy and safety studies are underway.

Safety and effectiveness of thalidomide and hydroxyurea combination in β‐thalassaemia intermedia and major: a retrospective pilot study

“…Several new treatment modalities including fetal globin gene reactivation, allogeneic haematopoietic stem cell transplantation (alloHSCT) and gene therapy are being explored to correct the disparity in α/β globin chains in thalassaemia (de Dreuzy et al , ). Fetal haemoglobin (HbF) expression could decrease ineffective erythropoiesis by reducing the build‐up and precipitation of α‐globin chains (Soni, ).…”

Theorizing Beta Thalassemia Major: an Overview of Health Sociology

“…The application of bio-psychosocial model in thalassemia can interpret the biological factors related to the thalassemia in the context of genetic vulnerability, disability and physical health while social factors includes awareness and knowledge about the disease and cultural practices for the understanding and propagation of thalassemia. Reviewing the literature showed that psychological aspects are only measured as impact of thalassemia on patients and their families (Baraz et al, 2016;Behdani et al, 2015;Mansoor et al, 2018), however genetic abnormalities (Brancaleoni et al, 2016;de Dreuzy et al, 2016) and socio-cultural factors (Sarvestani et al, 2019;Seyedifar et al, 2016) are the major risk factors of thalassemia propagation.…”

Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches

“…However it is still limited in developing countries because of the lack of equipment and the very expensive cost. [45]. This has been formalized by the classification Lucarelli who, depending on the presence or not of the 3 Risk factors that are hepatomegaly, portal fibrosis and insufficient chelation, classifies patients into three risk classes for transplant success [46] ( (class 1= no risk factor, class 2 =one or two risk factors and class 3= three risk factors).…”