Gene therapy for the treatment of primary immunodeficiency diseases received a setback this month with the announcement that a three-year-old boy taking part in a French trial has developed leukaemia (Reuters).

The child, who suffers from X-linked severe combined immunodeficiency disease (X-SCID), was enrolled in a trial run by Alain Fischer at the Hôpital Necker in Paris. The therapy involves retroviral expression of the common cytokine-receptor γ-chain (γc) in haematopoietic progenitor cells of the patient, which restores signalling downstream of γc-containing receptors (see the article by A. Fischer, S. Hacein-Bey and M. Cavazzana-Calvo in the August 2002 issue of Nature Reviews Immunology). In this case, the virus seems to have “delivered its payload directly into a gene called LM02” (Washington Post) — modifications of this gene are linked to the development of cancers of the blood.

The French trial has been suspended pending further investigations (The Guardian), and scientists in the United States have recommended that similar studies proceed, but with some restrictions (New York Times). Related studies in the United Kingdom will continue, and Adrian Thrasher, from The Institute of Child Health, London, told us, “on current evidence from animal and human studies we still believe that the risk [of insertional mutagenesis] is very low, but we will only really be able to define this by treating more patients, and by characterizing the type and number of integration events”.

Meanwhile, Californian scientists have offered a ray of hope for future gene-therapy trials — they have developed a plasmid-based method to target genes for insertion at specific sites in the genome (Nature Biotechnology DOI 10.1038/nbt753).