Scientists have confirmed that gene therapy treatment was the cause of leukaemia-like symptoms in two boys who underwent treatment for X-linked severe combined immunodeficiency disease (X-SCID) at the Necker Hospital in Paris.
In May 2000, the hospital first reported successes using gene therapy to treat X-SCID, a single gene disorder affecting only boys. In the UK in 2001, Rhys Evans, another boy with the disease, was successfully treated using gene therapy at Great Ormond Street Hospital in London.
However, trials in France and the US were suspended last October after one of the boys being treated in Paris developed leukaemia-like symptoms. French public health officials ordered a halt to the trials while they investigated and the decision was quickly mirrored in the US. The boy who had developed leukaemia had received gene therapy in the first month of his life, and seemed to respond well to the treatment. But he began to show leukaemia-like symptoms in August 2002.
In December 2002, investigations by the French team indicated that the virus used to transfer the therapeutic genes into the patient had managed to insert itself into a gene called LMO2. The activation of this gene, previously linked to leukaemia, was initially thought to have triggered his cancer. However, further studies showed that the boy had relatives affected by childhood cancer, so he may have had a higher risk of developing leukaemia before starting the gene therapy.
In January, news that a second gene therapy patient at the Necker Hospital was showing symptoms of leukaemia caused the US Food and Drug Administration (FDA) to suspend a further 27 trials that used the same gene delivery system as the experimental X-SCID treatment. The UK's Gene Therapy Advisory Committee (GTAC) did not halt the X-SCID trial taking place in London, but said that no new patients would be treated until the evidence from the French trial has been examined. Now, at a conference of the European Society of Human Genetics, Dr Hacien-Bey-Abina of the Necker Hospital team has confirmed the original suspicions about the first boy, adding that in the second, the virus had landed 'near' the LMO2 gene. But she reminded the conference that 'all the patients except patient four and five are doing well. They are healthy and they are at home'.
Sources and References
Cancer said side effect of gene therapy
Gene therapy led to cancer cases