A paradigm shift on beta-thalassaemia treatment: How will we manage this old disease with new therapies?

Beta-thalassaemia causes defective haemoglobin synthesis leading to ineffective erythropoiesis, chronic haemolytic anaemia, and subsequent clinical complications. Blood transfusion and iron chelation allow long-term disease control, and haematopoietic stem cell transplantation offers a potential cure for some patients. Nonetheless, there are still many challenges in the management of beta-thalassaemia. The main treatment option for most patients is supportive care; furthermore, the long-term efficacy and safety of current therapeutic strategies are limited and adherence is suboptimal. An increasing understanding of the underlying molecular and cellular disease mechanisms plus an awareness of limitations of current management strategies are driving research into novel therapeutic options. Here we provide an overview of the current pathophysiology, clinical manifestations, and global burden of beta-thalassaemia. We reflect on what has been achieved to date, describe the challenges associated with currently available therapy, and discuss how these issues might be addressed by novel therapeutic approaches in development.