X-linked lymphoproliferative disease (XLP) is a rare, severe genetic illness that affects the immune system. Affected boys typically become sick during childhood or early adolescence – and sadly, without a bone marrow transplant, they will usually lose their lives. Professor Claire Booth at the UCL Great Ormond Street Institute of Child Health is aiming to develop a new treatment using cutting-edge gene editing technologies to correct the faulty gene in a child’s blood stem cells. Building on previous work in this area, this exciting new approach has the potential to cure the disease by repopulating their immune system with healthy cells – saving lives and preventing illness in boys born with XLP.

How are children’s lives affected now?

Caused by faults in a single gene, boys born with XLP have an increased risk of developing life-threatening infections and some will develop a type of cancer caused lymphoma. Currently, the only available treatment is a bone marrow transplant – but the outcome will depend on finding a well-matched donor and carrying it out before any symptoms develop.

“Unfortunately, a successful transplant isn’t always possible – it may happen too late or a suitable donor can’t be found,” says Professor Booth.

Gene therapy, which involves inserting a correct copy of the gene into the patient’s own blood cells in the laboratory before transplanting them back into their body, offers hope of a new cure for XLP that doesn’t involve waiting for a donor.

“However, the conventional approach inserts the gene into a random location in the patient’s genome and, unlike in healthy people, it is permanently switched on – which could lead to unwanted effects,” says Professor Booth.

How could this research help?

“Our goal is to use newer targeted gene editing technologies to develop a safer way to cure boys with XLP,” says Professor Booth.

The team is building on previous work where they have shown they can use gene editing to correct the faulty gene in its natural location in white blood cells collected from patients, restoring normal gene activity and cell function.

“We will now use this approach to correct the faulty gene in patient blood stem cells,” says Professor Booth. “As these can develop into all types of blood cells, this could offer a curative treatment.”

After perfecting their gene editing techniques, the researchers will then transplant corrected patient blood stem cells into a laboratory model to find out whether they can generate a fully functional immune system.

“If our results are promising, this could pave the way to a clinical trial and lead to an exciting new treatment for boys with XLP – and accelerate progress towards similar cures for other serious genetic diseases,” says Professor Booth.

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