A boy enrolled on a pioneering gene therapy trial has developed leukaemia, his doctors based at London's Great Ormond Street Hospital have announced. The three-year-old was of one of 10 patients treated for X-linked severe combined immunodeficiency (X-SCID): a genetic disorder whereby a mutation in the IL2RG gene leaves carriers without a functioning immune system.
Leukaemia is, however, an 'acknowledged risk of the treatment', says Professor Bobby Gaspar, a consultant immunologist involved in the trial. As such, this is a setback for the trial but no hammer blow for the much-maligned field of gene therapy.
Gene therapy works by replacing defective genes in a specific tissue with fully functioning copies. Non-harmful viruses are employed as a means to deliver functional genes into the cell. Current thinking suggests that the insertion of viral DNA into the human genome, integral to this process, is inappropriately 'switching on' oncogenes: genes that when functioning incorrectly have the ability to turn a cell cancerous.
X-SCID is often dubbed in the press 'baby in the bubble' syndrome, because carriers have to reside in a sterile environment to avoid infection, and unless a suitable bone marrow donor can be found there is no alternative treatment. Carriers can often die within a year without intervention. This leaves patients little choice other than to seek help from gene therapy trials and their associated risks. 'All these children have a potentially fatal disease, and we have to remember that. All families were counselled as to the risks, and so far, this development has been the only negative one', said Professor Gaspar.
A similar French trial was placed on hiatus three years ago after three of its 11 patients developed leukaemia - one died. Studies performed in mice last year appeared to confirm the link. However, despite a number of gene therapy trials ongoing worldwide - for example, 12 different cancers, heart disease and Parkinson's disease are all in phase III trials - the induction of leukaemia in gene therapy trialists appears to be limited to X-SCID patients and the type of viral vectors utilised in those studies. 'The fact is, the only leukaemias that have occurred are in these children out of the 1,300 people who have undergone gene therapy', said Professor Martin Gore, chairman of the Gene Therapy Advisory Committee (GTAC), a UK national research ethics committee.
The second generation of X-SCID gene therapy trials have been informed by these developments. For Great Ormond Street's next trial, due to kick-off in the middle of 2008, a vector has been developed which even if implanted next to an oncogene will not switch it on. 'We are confident that this new treatment will not pose the risk of leukaemia, as it does not seem to switch on the gene which causes it', says Professor Gaspar.