Thalassemia is a group of genetic disorders affecting 280 million people worldwide. The body produces insufficient functional haemoglobin – the protein in red blood cells that carries oxygen through the body – resulting in anaemia and, consequently, shortness of breath and tiredness. Most patients need monthly blood transfusions which are costly and can have severe side effects.
'The standard procedure for a curative option for thalassemia would be a bone marrow transplant from a brother or sister, which is not without significant risk, but more importantly, most people will not have that appropriate sibling donor,' said Dr Alexis Thompson at the Ann & Robert H. Lurie Children's Hospital of Chicago in Illinois, who led the trial.
The new gene therapy treatment developed by Bluebird Bio based in Seattle, Washington, was trialled in 22 beta-thalassemia patients, aged 12 to 35. Stem cells from each patient's bone marrow were collected and a functional version of the HBB gene (in which people with beta-thalassemia carry a mutation), was inserted into the cells using a viral vector. The cells were then transfused into the patient's bone marrow in the attempt to start producing red blood cells with fully functioning haemoglobin.
Of the 22 patients, 15 (three of whom had a severe form of the disease) no longer needed monthly blood transfusions. For the remaining patients, most needed fewer or smaller transfusions – the average reduction was 73 percent. The study was published in the New England Journal of Medicine.
'Relatively speaking, this procedure was well-tolerated by the patients, with no unexpected toxicities related to gene therapy,' said Dr Thompson. Discussing applying the method to other diseases like sickle cell, she said: 'This approach may be effective. It has been safely done and should open doors for other diseases like sickle cell.'
Professor Douglas Higgs, at the MRC Haematology Unit, University of Oxford, who was not involved in the study, welcomed the research. But he cautioned: 'We still do not know the long-term effects of manipulating the genome of stem cells in this way.'
'A major question hanging over this approach, which is hugely expensive, is whether this procedure, which involves killing off abnormal stem cells to replace them with modified stem cells, will ever become clinically possible in developing countries where the majority of these disorders of haemoglobin occur,' he said.