BioWorld International Correspondent

LONDON - One of 10 children given gene therapy for the X-linked severe immunodeficiency disorder, X-SCID at Great Ormond Street Hospital, London, has developed leukemia two years after treatment.

That acknowledged risk of the treatment brought an end to a similar trial at the Necker-Enfants Malades Hospital in Paris, where the technique was developed, in 2002. The trial in Paris was claimed to be the first successful example of gene replacement therapy, but four of 11 children treated here subsequently developed leukemia.

All the children treated in London, "have seen clinical benefit" according to Adrian Trasher and Bobby Gaspar, the immunologists running the program.

The gene therapy replaces the defective IL2RG gene, which controls a protein involved in the development of B and T cells of the immune system. Prior to the development of the treatment, children who did not have a bone marrow donor only could survive by living within sterile bubbles.

Leukemia is thought to be initiated when the inserted gene activates an oncogene.

But a joint U.S. and German study published in 2006 showed that transfecting IL2RG into mice caused one-third of them to develop leukemia, implying that the corrective gene itself contributed to the development of the disease.

The doctors at Great Ormond Street have alerted the UK's Gene Therapy Advisory Committee, (GTAC), which oversees such trials. The chair of GTAC, Martin Gore, noted that families are counselled extensively on the risks of the treatment, and that the gene therapy has given much hope to children with fatal immunodeficiency diseases.

GTAC previously put the London trial on hold when the children in the French trial developed leukemia. It was allowed to restart on the grounds that leukemia is a known risk and it would be wrong to stop the trial, as the children would die without treatment. The trial now is fully recruited.

Trasher and Gaspar are working to refine the existing treatments, and Gore said, "New gene therapy vectors for future trials should work better with fewer side effects.

"The data GTAC has seen from both the UK and French trials suggest that the risk of leukemia following gene therapy may be confined to this patient group and the particular vectors used in the these two trials," he added.