Abstract
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
solely relies on repeated transfusions followed by iron chelating
therapy which can eventually results into multi-organ damage. A number
of novel approaches to correct the resulting α/β globin chain imbalance
are currently being developed. These include reactivation of foetal
haemoglobin by pharmacological compounds, allogenic hematopoietic stem
cell transplantation (HSCT) and gene therapy. Up to now, the only
curative treatment for beta-thalassemia is HSCT, but this is a risky and
costly procedure. Gene therapy either by gene addition or gene editing
is emerging as a powerful approach to treat this disease. Gene addition
is currently based on transplantation of autologous hematopoietic stem
cells genetically modified with an integrating lentiviral vector
expression the globin gene while gene editing involves the use of
CRISPR/Cas9 to correct the causative mutation. Although the early
outcomes of the clinical trials in gene therapy are showing promising
results, they have also highlighted a number of limitations. In this
review we will discuss about the current management strategies used to
treat beta-thalassaemia and also focus on novel therapies.