Blood disorder cured – a first for gene therapy

A 21-YEAR-OLD Frenchman is the first person in the world to be cured of the blood disorder beta-thalassaemia through gene therapy. But there is some confusion over what made the treatment work.

Before gene therapy he needed monthly blood transfusions to provide him with beta-globin, a key component of the haemoglobin molecule that carries oxygen around the body. He has now been transfusion-free for over two years.

Philippe Leboulch of the University of Paris, France, and Harvard Medical School in Boston, infected stem cells from the man's bone marrow with a harmless virus, which transferred perfect copies of the beta-globin gene into the DNA of the extracted cells.

Returned to the patient, these cells now contribute about a third of his beta-globin, with his body producing the rest. Although the treatment had the desired effect, the proliferation of the altered cells could be down to the activation of a different gene, HMGA2, switched on by accident during the DNA transfer.

One worry throughout the history of gene therapy is that viruses transferring beneficial genes will accidentally activate other genes that could trigger cancer. This happened in four French boys treated for the immune deficiency, X-SCID, who developed leukaemia. One died and the others recovered after treatment.

"We must be very cautious, but the signs are that the impact of the HMGA2 gene will be benign," says Leboulch.

After more detailed analysis, the team found other cells producing beta-globin that do not have the HMGA2 gene switched on. Leboulch concludes that it is unlikely the HMGA2 gene by itself is responsible for the survival of the beta-globin-producing cells.