Beta-thalassemia is an inherited blood disease. It is caused by a fault in the HBB gene. As a result, patients have low levels of haemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body. In the most severe cases, haemoglobin levels are so low that patients require regular blood transfusions. Therefore, the disease is referred to as “transfusion-dependent beta-thalassemia”. Beta-thalassemia is one of the most common genetic diseases: each year, approximately 25,000 babies are born with transfusion-dependent beta-thalassemia and there are more than 200,000 patients worldwide with the disease (sources: Modell 2008; Williams 2012).
Patients with transfusion-dependent beta-thalassemia need frequent blood transfusions to replenish the level of haemoglobin in their red blood cells. However, because of these regular transfusions, iron accumulates in various organs over time, leading to risk of heart or liver failure. Therefore, patients who receive ongoing blood transfusions must also take medicines to remove the excess iron. These medicines, called iron chelation therapies, also have side effects and can negatively impact a patient’s quality of life. As an alternative to regular blood transfusions, patients with transfusion-dependent beta-thalassemia can receive a bone marrow or cord blood transplant. This procedure can be curative, but it carries a risk of mortality and morbidity, especially where there is not a good match between the donor and the patient.
Doctors and scientists have invented a potential new way of treating transfusion-dependent beta-thalassemia called "autologous ex vivo gene therapy". This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing HBB gene (or ß-globin gene). These genetically modified stem cells are then given back to the patient via an intravenous infusion in a procedure referred to as "hematopoietic stem cell transplant". After the stem cells are given back to the patient, they can grow and divide into new cells that produce increased levels of haemoglobin.