Uncertain future for gene therapy

Gene therapy trials for a rare inherited immune disease might be allowed to proceed, but only for patients with no other treatment options, a US advisory panel concluded at an emergency meeting last week. The Recombinant DNA Advisory Committee (RAC) also said that resuming trials for other diseases 'may be justified', with appropriate patient information and monitoring.

Gene therapy trials for X-linked severe combined immune deficiency (X-SCID) were suspended in the US and several other countries recently, after two patients in a French trial developed leukaemia. The US Food and Drug Administration (FDA) also suspended 27 other trials that use the same gene delivery system as the experimental X-SCID treatment. Children affected by SCID have a faulty gene that means they have no working immune system, so their bodies cannot fight infections.

Scientists at the Necker Hospital in Paris treated eleven X-SCID patients by delivering a working gene to the immune cells in the bone marrow. Nine responded well to the treatment, but two of them subsequently developed symptoms of the blood cancer. Investigations revealed that the virus used to deliver the therapeutic gene had inserted itself into or close to another gene called LMO2, previously linked to leukaemia. The RAC heard last week that a third patient in the French trial has immune cells with a gene insertion near LMO2, although he has no symptoms of leukaemia. This serious potential side effect was 'not a random event' and constitutes a 'serious inherent risk', the RAC concluded. However, the panel also heard from researchers arguing that other trials, such as those for adults with life-threatening tumours, should be allowed to resume.

An FDA advisory committee is to review the safety data and consider the future of X-SCID gene therapy and similar trials when it meets on 28 February. The X-SCID trial taking place at Great Ormond Street Hospital in London remains suspended, pending a joint meeting of the UK's Gene Therapy Advisory Committee and the Committee on the Safety of Medicines in March.