Scientists discover cause of leukaemia that halted treatment trial for ‘Baby–in–a–bubble’ Syndrome

17th October 2003

Medical Research Council (MRC) scientists have helped establish the cause of the leukaemia which developed in two young patients taking part in a pioneering gene therapy trial to treat the fatal 'baby-in-a-bubble' syndrome, severe combined immunodeficiency (X-SCID).

The trial at the Necker-Enfants Malades clinic in Paris was stopped last year due to the higher than expected number of cases of leukaemia amongst the eight children taking part. After three years of successful gene therapy for X-SCID, leukaemia occurred in the two youngest patients undergoing treatment.

Contributing to the international effort to establish quickly why the leukaemia developed, the scientists reveal in the journal Science that in the cases of the two boys, the gene therapy corrected the faulty gene but also activated a cancer-causing gene called LMO2.

The scientists suggest that a number of factors might explain why this occurred at a very much higher frequency than expected and that by modifying these factors, scientists will be able to deliver a gene therapy to treat X-SCID which has a much lower risk of causing leukaemia.

X-SCID is a genetic disease only found in boys. Those with X-SCID, or ‘baby-in-a-bubble’ syndrome, are born without an immune system forcing them to live in sterile conditions or risk picking up a life-threatening infection. The disease is caused by a single mutated gene and in the absence of a matched bone marrow donor there is no cure other than gene therapy.

Lead MRC researcher, Dr Terry Rabbitts of the MRC Laboratory of Molecular Biology, said: “Cancer is a possible side effect of gene therapy, so any research which will help scientists to modify the treatment to reduce that risk is of great importance. Although it is anguishing for parents to expose their children to the chance of developing cancer, the benefits of gene therapy for this devastating disease greatly outweigh the risks of the disease itself as X-SCID can only be treated if a matched bone marrow donor is available.”

Both children who developed leukaemia during the trial underwent treatment for their cancer with chemotherapy and bone marrow transplants. They are alive and well, and in complete clinical remission.

Up to one in 50,000 births in the UK are affected by X-SCID.

Dr Rabbitts worked on this project in collaboration with scientists from the Babraham Institute and across Europe and the USA

For further information, or to arrange an interview with Professor Rabbitts, contact the MRC Press Office on 020 7637 6011.

Notes to Editors

Dr Peter Fraser and Dr Cameron Osborne from the Babraham Institute produced visual evidence that the leukaemia-causing gene (LMO2) was activated by the x-SCID gene therapy, using a technique called RNA-FISH (Fluorescence In Situ Hybridisation). In this method, DNA probes are tagged with fluorescent markers and mixed with the cell. The probes bind to RNAs produced at the target genes if the target gene is activated. The fluorescent tags indicate the genes' location when the cell is studied under UV light microscopy.

Dr Peter Fraser is Head of the Nuclear Dynamics ISP at the Babraham Institute. He is an MRC Senior Fellow.

The Babraham Institute is a charitable organisation, which receives strategic funding from the Biotechnology and Biological Sciences Research Council, carrying out scientific research to find new medicines and treatments for premature babies and people suffering from conditions such as cancer, rheumatism, Alzheimer's disease and strokes. Babraham's scientists are striving to find cures for conditions where there is currently no treatment or where the existing treatment is not fully effective or causes serious side effects. Babraham is located six miles south-east of Cambridge.

The Medical Research Council (MRC) is a national organisation funded by the UK tax-payer. Its business is medical research aimed at improving human health; everyone stands to benefit from the outputs. The research it supports and the scientists it trains meet the needs of the health services, the pharmaceutical and other health-related industries and the academic world. MRC has funded work which has led to some of the most significant discoveries and achievements in medicine in the UK . About half of the MRC's expenditure of over £413 million is invested in its 40 Institutes, Units and Centres, where it employs its own research staff. The remaining half goes in the form of grant support and training awards to individuals and teams in universities and medical schools.
MRC web site