Institute of Child Health

Papers published today in Science Translational Medicine report success in two established gene therapy programmes to cure children born unable to fight infection.

The programmes, which looked at X-SCID and ADA-SCID, were led by Professors Adrian Thrasher and Bobby Gaspar of the UCL Institute of Child Health (ICH).

14 out of 16 patients across the two programmes were successfully treated.

The work was funded by Great Ormond Street Hospital Children’s Charity, Wellcome Trust, The Primary Immunodeficiency Association and the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital.

In the treatment of X-SCID, commonly known as ‘boy in the bubble’ syndrome, ten out of ten patients show clear clinical benefits and have no social restrictions1. One child regrettably developed leukaemia and is currently in remission2. As a result, safer vectors were developed and are now being used.

X-SCID is caused by mutations in the IL2RG gene, which governs the behaviour of a protein involved in the development of a number of immune system cells.

In a programme looking at ADA-SCID, four out of six children treated show clear clinical benefit and have no social restrictions. ADA-SCID results from the lack of an enzyme that helps cells to get rid of toxic byproducts.

Children involved in both programmes continue on some medication, but five of the ten X-SCID and three of the four ADA-SCID patients no longer take immunogloblins.

Professor Thrasher, consultant in paediatric immunology and X-SCID programme lead said: “These are excellent results for our gene therapy programmes and the first time we have been in a position to say we have found a cure for patients with these conditions. It demonstrates that gene therapy for immune diseases is now mainstream, and we hope this approach will benefit many more of our patients in the future.”

Professor Gaspar, consultant in paediatric immunology and ADA-SCID programme lead said: “We are delighted by the results of both of these programmes.

“The success of the ADA-SCID programme has also saved the NHS millions of pounds, as these children are able to stop receiving regular costly enzyme replacement injections.

“Worldwide, 30 children have received gene therapy for ADA-SCID, none of whom have died and 70 per cent of whom have seen a clear clinical benefit.

“We are now leading trials for two other immune disorders with colleagues from across the globe, and hope that gene therapy will now be seen as a standard alternative to conventional treatments such as bone marrow transplant.

“We also hope to be able to extend this approach to other conditions, such as lysomal storage diseases, where a metabolic fault means chemicals build up in cells and cause various problems throughout the body.

Gaynor Harnden’s son Guy, 6, was enrolled on the X-SCID programme. She said: “Guy is now doing brilliantly, he can do all of the things his friends can and more. He is able to play football and ride a pony.

“He wouldn’t be here if it wasn’t for the option of gene therapy treatment. We are incredibly grateful to the whole team at Great Ormond Street Hospital, but especially Adrian Thrasher and Bobby Gaspar who pioneered this work. To other parents who find themselves in our situation we would say ‘go for it’”.

Great Ormond Street Hospital runs more gene therapy trials for immune deficiency in children than any other centre in the world. The papers come over a decade after Rhys Evans became the first boy to be successfully treated for X-SCID by gene therapy at the hospital. The first patient to undergo ADA-SCID treatment is now almost eight years post gene therapy.