Rare immune disease treated successfully with personalised gene therapy

A world-first gene therapy has successfully been used to restore the immune system of a teenager with a rare genetic condition.

P47 chronic granulomatous disease (CGD) is an inherited immunodeficiency disorder, affecting just one in a million people in the world. P47 CGD is caused by mutations in the NCF1 gene, which is needed to form a key component of NADPH-oxidase – an enzyme that is responsible for killing bacteria and fungi. Without this enzyme, the immune system does not function properly, leaving people with P47 CGD more susceptible to frequent fungal and bacterial infections. Now, researchers at University College London (UCL) and Great Ormond Street Hospital for Children (GOSH) have developed, manufactured and delivered a new personalised gene therapy treatment for P47 CGD. The patient, Remi, received the treatment in June 2024.

'For the first time we've been able to develop, manufacture, and deliver a new gene therapy entirely under one roof – marking a true bench-to-bedside milestone,' said Professor Claire Booth, consultant paediatric immunologist at GOSH, and the trial's principal investigator. 'This is a significant step forward. It means that future gene therapies developed at UCL and GOSH could reach clinical trials, and patients with rare diseases like Remi, faster than ever before.'

The standard treatment for P47 CGD is an allogeneic haematopoietic stem-cell transplantation (HSCT) – commonly known as a bone marrow transplant – but it can be challenging to find a matching donor. For the new gene therapy treatment, researchers collected haematopoietic stem cells from Remi's bone marrow, which were fused with a functional copy of the NCF1 gene using a lentiviral vector. These were then administered back to the patient, leading to the delivery of a functional copy of the NCF1 gene into the cells' genome.

Within weeks, Remi began to produce healthy immune cells capable of fighting infections. Unlike a bone marrow transplant, there is no risk of rejection with the new autologous treatment, as his own stem cells were used.

Remi, who is now 19, commented: 'Having the gene therapy has completely changed my life. I can go out and about now without worrying, help my family out and I'm excited to start university and start the next stage of my life.'

The researchers hope to treat four other children with P47 CGD as part of the clinical trial.

Professor Booth concluded: 'We've demonstrated the technology works… In the future with genome sequencing at birth, you could identify a treatable condition and have personalised medicine for it.'

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The availability of genetic and genomic testing for people and families affected by rare disease will be discussed at the free-to-attend online event Rare Disease Genomic Testing: How Do We Make Access Equitable and Timely?, taking place online on Wednesday 22 October 2025.

Find out more and register here.