Page URL: https://www.bionews.org.uk/page_90006

X-SCID gene therapy cancer risk in mice

27 April 2006
By BioNews
Appeared in BioNews 356

Replacement genes used to treat an inherited immune disorder could trigger cancer, new research carried out on rodents suggests. The study, published in the journal Nature, shows that treating mice with a normal copy of the gene defective in X-linked severe combined immune deficiency (X-SCID) results in cancer of the white blood cells in a third of the animals. The scientists say that the study highlights the need for longer-term follow-up in studies designed to test the safety of new gene therapy treatments. However, UK gene therapy researcher Adrian Thrasher says that the results could have been caused by artificially high levels of the gene in the animals.

The team, based at the Salk Institute for Biological Studies in La Jolla, California, say their findings could help explain one of the three cases of leukaemia in a French X-SCID gene therapy trial. Two of the cases are thought to have arisen after the therapeutic gene activated a gene known to be involved in cancer, but the new study suggests that the therapeutic gene itself may also pose a risk. The researchers followed mice treated with the IL2RG gene - which is missing or faulty in people affected by X-SCID - and followed them up for 18 months, three times longer than any previous study. They found that a third of the animals developed cancer of the white blood cells, at an average age of ten months. 'These results suggest that curing X-SCID by replacing IL2RG in the manner it is currently being done puts patients at an increased risk of developing cancer', said team member Niels-Bjarne Woods.

Ten patients affected by X-SCID have so far been treated in the French trial, based at the Necker Hospital in Paris. While most have responded extremely well to the therapy, the trial was halted for a second time in January 2005, after a third patient developed symptoms of leukaemia. Two of the affected boys are now in remission, but the other died, and the trial is currently continuing on a case-by-case basis. Children affected by SCID have a faulty gene that means they have no working immune system, so their bodies cannot fight infections. This life-threatening condition is sometimes called 'bubble boy' disease as, unless they can be successfully treated with a matched bone marrow transplant, patients must spend their lives in a sterile environment.

Woods says that the new study could help explain the occurrence of leukaemia in one of the French patients, in whom the therapeutic gene did not activate a cancer-causing gene. In the affected mice, the IL2RG gene inserted itself at different places in the animals' DNA, ruling out the possibility that any cancer genes had been activated. The fact that the leukaemia did not appear until 2-3 years after the gene therapy treatment suggests that 'preclinical experimental treatments involving transgenes should include long-term follow-up before entering a clinical trial', says Woods. He also says that replacing a faulty gene that has multiple effects in the body may prove much more problematic than replacing a gene with a single main role.

Mark Kay, a US gene therapist based at Stanford University says that 'the results are significant and need to be considered in the design of future gene therapies'. However, he also sees a continuing need for SCID trials for patients with no other treatment options, ScienceNOW reports. But UK researcher Adrian Thrasher told the Daily Telegraph newspaper that the data is 'very preliminary', and the effects could be down to 'artificially high levels of the gene in the animals'. Thrasher, who runs the X-SCID trial based at Great Ormond Street Hospital in London, added that 'certainly we and our colleagues have found no evidence for this effect'.

SOURCES & REFERENCES
Don't Blame the Messenger
Science Now |  26 April 2006
Gene transplant 'cancer risk'
The Daily Telegraph |  27 April 2006
Mouse study reveals human X-SCID gene therapy poses substantial cancer risk
EurekaAlert |  26 April 2006
RELATED ARTICLES FROM THE BIONEWS ARCHIVE
30 October 2017 - by Jen Willows 
NICE has approved a gene therapy for children with a rare disorder that leaves them with no functioning immune system...
13 October 2014 - by Dr James Heather 
Gene therapy to treat children with 'bubble boy syndrome' seems to be both safe and effective, a study published in the New England Journal of Medicine has found...
30 August 2011 - by Rosemary Paxman 
Over a dozen children with 'boy in bubble' syndrome are alive and well, with functioning immune systems, nine years after undergoing gene therapy to correct their disorder, researchers report....
15 November 2010 - by Chris Chatterton 
Doctors from Great Ormond Street Hospital (GOSH) have used stem cells from donated cord blood to treat a child with a rare genetic disorder....
2 February 2009 - by Dr Megan Allyse 
Researchers in Italy and Israel have announced that they have successfully used gene therapy to treat ten children who suffer from a rare form of severe combined immunodeficiency (SCID) called ADA-SCID. The trial marks one of the first successful uses of gene therapy since past trials of...
7 March 2005 - by BioNews 
The US Food and Drug Administration (FDA) has recommended that gene therapy treatments for an inherited immune disorder are limited to those who have no alternative. The move follows news that a third child in a similar French trial has developed leukaemia. The trial for X-linked severe combined immunodeficiency disorder...
31 January 2005 - by BioNews 
A gene therapy trial for an inherited immune deficiency disorder has been suspended again, following the appearance of complications in a third child. Eleven patients affected by X-linked severe combined immunodeficiency disorder (X-SCID) have so far been treated by the team, based at the Necker Hospital in Paris. While most...
17 December 2004 - by BioNews 
Four children who received gene therapy for a severe inherited immune disorder are now all at home living normal lives, UK scientists report. The boys, who were affected by severe combined immunodeficiency (SCID), received the pioneering treatment at Great Ormond Street Hospital in London. In a commentary accompanying the study...
14 June 2004 - by BioNews 
A French gene therapy trial halted after two participants developed leukaemia looks set to restart after a 22-month suspension, reports Nature. Scientists at the Necker hospital in Paris successfully treated nine children with an inherited immune system disorder called X-linked severe combined immune deficiency (X-SCID). But the trial, along...
17 October 2003 - by BioNews 
US and European scientists have published results confirming that a gene therapy technique triggered leukaemia in two boys taking part in a trial at the Necker hospital, Paris. Their findings, which appear in Science, show that the virus used to deliver the therapeutic gene activated a cancer-causing gene. Eleven boys...
HAVE YOUR SAY
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions


Syndicate this story - click here to enquire about using this story.