Long-term gene therapy success for children with rare immunodeficiency

Follow-up of gene therapy-treated children born with an immune disorder has confirmed the treatment is safe and 95 percent effective.

ADA-SCID (severe combined immunodeficiency from adenosine deaminase deficiency) is a rare genetic condition that leaves children without a functional immune system due to a mutation in the ADA gene. Between 2012 and 2019, 62 affected children received an experimental gene-therapy treatment at Great Ormond Street Hospital in London or in the USA. This involved using a non-harmful virus to deliver a functional copy of the gene into stem cells temporarily removed from their blood and bone marrow.

'Treatment was successful in all but three of the 62 cases, and all of those children were able to return to current standard-of-care therapies,' said senior author Professor Donald Kohn, from the University of California, Los Angeles. 'These results are what we hoped for when we first began developing this approach. The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging.'

ADA-SCID affects around one in 200,000 children, and without treatment can be fatal within the first two years of life. Typical treatment is expensive and restrictive, involving a bone marrow transplant or weekly injections of the functional ADA enzyme and avoiding day-to-day activities like going to school, to minimise risk of exposure to infections.

Now, 59 gene-therapy-treated children have remained disease-free over an average of 7.5 years, returning to normal life without side effects like increased risk of cancer that have been seen in some other gene therapies. The report, published in the New England Journal of Medicine, also revealed that many of the children even responded to routine childhood vaccinations such as tetanus or measles, mumps, and rubella (MMR) – something that was previously impossible for them.

Previous work explored why three of the children did not respond to the gene therapy, revealing that there is a minimum number of cells needed to be treated (see BioNews 1118).

'Our goal is to have this therapy FDA-approved within two to three years,' said Professor Kohn. 'The clinical data strongly supports approval – now we need to demonstrate that we can manufacture the treatment under commercial pharmaceutical standards.'

Co-first author Professor Claire Booth, from University College London and GOSH, pointed out the wider implications of their findings: 'This is also very reassuring for other conditions treated using the same techniques – showing that it works in the long term and is safe.'

The mother of an 11-year-old girl who received the treatment as a baby said: 'I am eternally grateful to every single scientist, doctor, lab worker, nurse, hospital security guard – all the people who had anything to do with this gene therapy coming into existence and saving her.'