Beta Thalassemia Major: Overview of Molecular Etiology, Pathophysiology, Current and Novel Therapeutic Approaches
S. El Kababi *
Laboratory of Physiopathology, Genetics Molecular and Biotechnology (PGMB), Faculty of Sciences Ain Chock, Research Center Health and Biotechnology, Hassan II University of Casablanca, Km 8 Route El jadida 5366, Mearif, 20100 Casablanca, Morocco and Higher Institute of Nursing and Health Thechnique Professions, Mohammed El Faidouzi Hospital, District 20670 Casablanca, Morocco.
B. El Khalfi
Laboratory of Physiopathology, Genetics Molecular and Biotechnology (PGMB), Faculty of Sciences Ain Chock, Research Center Health and Biotechnology, Hassan II University of Casablanca, Km 8 Route El jadida 5366, Mearif, 20100 Casablanca, Morocco.
K. El Maani
Department of Hematology-Oncology Pediatric, Thalassemia and Haemopphilia Center, Children's Hospital Abderrahim Harouchi, Ibn Rochd CHU Casablanca, Morocco and Faculty of Medicine and Pharmacy of Casablanca, Hassan II University, Tarik Bnou Ziad Street, 20360 Casablanca, Morocco.
A. Soukri *
Laboratory of Physiopathology, Genetics Molecular and Biotechnology (PGMB), Faculty of Sciences Ain Chock, Research Center Health and Biotechnology, Hassan II University of Casablanca, Km 8 Route El jadida 5366, Mearif, 20100 Casablanca, Morocco.
*Author to whom correspondence should be addressed.
Abstract
Major beta thalassemia is a severe form of thalassemia caused by the alteration of two beta globin genes resulting in a defective synthesis of hemoglobin.
It is characterized by chronic severe anemia, ineffective erythropoiesis (IE) and iron overload. However although the thransfusion and chelation assosciated constitute the basis of the traitement curently recommended, they do not allow always to control the iron overload induced by pathology and repeated transfusions.
Hematopoietic stem cell transplantation (HSCT) has proven to be a definitive treatment for beta thalassemia. However, this procedure is confronted to immunological complications and the small nomber of histocompatible donors. In the face of these therapeutic blocks, much research has been undertaken in recent years leading to the development of a number of promising therapeutic strategies in order to reduce the constraints linked to current chronic treatments, and to move towards an access to healing for all patients. Among other three approaches are envisaged and are in the experimental phase: Gene therapy to restore globin chain imbalance, Improve ineffective erythropoiesis and Improve iron dysregulation. In this article we give a view on the pathophysiology, clinical manifestations, genetic origin of beta-thalassaemia major. The second part presents the therapeutic arsenal currently used, and its limits leading to therapeutic impasse. The last part explores the scientific tracks that present a real therapeutic potential in β-Thalassemia.
Keywords: Thalasaemia, ineffective erythropoiesis, chronic haemolytic anaemia, blood transfusion, iron overload, novel therapies.