December 18, 2007

scientists react to news that a child receiving gene therapy has developed leukaemia

The three-year-old boy had been successfully treated at Great Ormond Street Hospital two years previously for X-SCID, a serious immune system disorder.

Professor Charles Coutelle of the National Heart and Lung Institute, Imperial College London, said:

“This is indeed a sad event although this child still has a good chance of recovery from this known risk factor of the particular treatment. This event, highlights, however, the urgent need to continue research to understand the molecular mechanisms, which cause such vector related leukaemia in some of the treated children in order to develop new and safer gene-transfer vectors and to minimise this risk in the future.”

Leonard Seymour, Professor of Gene Therapies, Department of Clinical Pharmacology, University of Oxford, said:

“The T cell leukaemia seen in one of the patients treated with gene therapy for SCID-X1 is extremely regrettable and our sympathies are with the child and his family as he undergoes chemotherapy. Scientifically, however, this was always a possible outcome following observation of similar leukamogenic effects in an equivalent study performed in France. It is nevertheless important to weigh the benefits of this pioneering treatment against the problems – X-linked SCID is a fatal disease and subjects without well matched bone marrow donors have no treatment alternatives. The use of gene therapy has given all the children extended high quality lives, free of their sterile incubators, providing the possibility of long term benefit and also increasing the time for finding a suitable marrow donor.

“Successful treatment requires the viral DNA to incorporate into the boys’s cellular DNA, however this can occasionally give rise to ‘insertational mutagenesis’ that leads to the leukaemia. Since we understood the problem, scientists have been developing safer ‘self-inactivating’ viruses that still insert into cellular DNA but are designed not to disturb it, achieving therapeutic benefit but avoiding the mutagenic effects. These agents are now being prepared ready for clinical study in the near future.

“The patients come first in all aspects of clinical trials, but these painful experiences teach us a great deal and are leading us scientifically towards more and more effective treatments that can ultimately provide safe cures for these lethal diseases.”