Gene therapy trials to resume

US gene therapy trials for a rare immune disorder, suspended after a patient in a similar French trial developed a leukaemia-like disease, should now go ahead, says the Recombinant DNA Advisory Committee (RAC). In October, gene therapy trials for severe combined immunodeficiency (SCID) were halted in several countries, after scientists at the Necker Hospital in Paris revealed that a three-year-old patient had symptoms of a leukaemia-like illness. SCID trials in Italy and Japan remain suspended, while in the UK, similar trials have continued uninterrupted following advice from the Gene Therapy Advisory Committee (GTAC).

The US Food and Drug Administration (FDA) concluded in October that the gene therapy was the likely cause of the leukaemia, and many trials using similar technology were halted. But the RAC has now concluded that the cancer was caused by a rare combination of factors, of which the gene transfer technique was just one.

Investigations by the French team, working with scientists in the US and Germany, show that the virus used to transfer therapeutic genes into the patient had managed to insert itself into a gene called LMO2. The subsequent activation of this gene, previously linked to leukaemia, was initially thought to have triggered blood cancer in the patient. However, further studies have also revealed that the boy had two relatives affected by a childhood cancer, so he may have had a higher risk of developing leukaemia before starting the gene therapy.

The RAC has advised that other SCID trials in the US should proceed, but with informed consent, and more long-term monitoring for signs of cancer. This advice mirrors that given by the UK's GTAC, which said that trials should continue, given the lack of alternative treatments for some SCID patients. Some gene therapy trials in Germany that use the same type of virus are also to resume, ending a moratorium introduced last June. The trials were halted following results from animal experiments, but will now be allowed to continue provided patients are made aware of the risks, and stand to benefit from the therapy.