What did the project achieve?
Building on earlier research funded by Action, Dr Claire Booth and Professor Bobby Gaspar, of the UCL Great Ormond Street Institute of Child Health, are aiming to develop a gene therapy to cure boys with a rare genetic illness called X-linked lymphoproliferative disease (XLP) that affects the immune system.
“We have now carried out extensive laboratory tests on our new gene therapy, with encouraging results,” says Dr Booth. “We have now planned a clinical trial in patients that should start in 2021.”
Boys with XLP have an increased risk of developing life-threatening infections and some will develop a type of cancer caused lymphoma. Currently, the only hope for a cure is a bone marrow transplant, but finding a well-matched donor isn’t always possible.
The researchers are aiming to develop a new curative treatment for XLP, which involves getting a healthy copy of the faulty gene into the patient’s own T cells – a type of white blood cell – and transplanting these back into their body.
“After optimising our techniques, we can now efficiently correct and expand T cells collected from XLP patients in the laboratory,” says Dr Booth.
The team has also shown that these corrected cells can improve some of the XLP disease symptoms in a laboratory model.
“The next step will be to transplant corrected T cells into boys with XLP in a clinical trial,” Dr Booth adds. “If successful, we hope our gene therapy will provide a new curative treatment that does not rely on finding a suitable bone marrow donor.”
This research was completed on
Building on earlier research funded by Action Medical Research, Professor Bobby Gaspar and Dr Claire Booth, of University College London’s Institute of Child Health, are moving one step closer to helping boys with a rare illness called X-linked lymphoproliferative disease (XLP). These boys typically become ill during childhood or early adolescence. Bone marrow transplants offer the chance of a cure if done early enough, but suitable donors can’t always be found. Sadly, without a transplant, the disease can be life threatening. Professor Gaspar’s team is in the laboratory stages of developing a much-needed new treatment for XLP, which might one day help spare children from ill health and save their lives.
Action Medical Research and Great Ormond Street Hospital Children's Charity are jointly funding this research.
How are children’s lives affected now?
“The first sign that boys with XLP have the disease often comes when they suffer a severe bout of glandular fever, which can be so serious it becomes life-threatening,” explains Professor Gaspar. “Symptoms vary though. Some boys develop a cancer called lymphoma and they can have difficulties fighting off other infections as well.”
Without treatment, around seven in every 10 boys with XLP would die by 10 years of age.1
“Medicines benefit boys with XLP and bone marrow transplants can be curative, but this means finding a donor who is a good match” says Professor Gaspar. “For transplants to work well, it’s best to carry them out early in the disease process.”
Sadly, if transplants come too late or donors cannot be found, boys with XLP remain at risk of losing their lives. Better treatments are needed urgently.
How could this research help?
“We are in the laboratory stages of developing a new treatment for XLP,” says Dr Booth. “Results of earlier studies, also funded by Action Medical Research, have been promising and the work we’re doing now will take us closer to the stage when clinical trials of our new treatment can begin in children.”
“XLP is a genetic disease,” continues Dr Booth. “We know which gene causes it and we know what that gene does. Our new treatment will involve putting a healthy copy of the gene into cells in the body that need it – an approach called ‘gene therapy’.”
Treatment will involve modifying cells called T cells from the child’s own immune system. In this project, the researchers aim to perfect their techniques and gather evidence on the safety and effectiveness of treatment in the laboratory.
Professor Gaspar and Dr Booth are optimistic: “We hope that experience gained in this study will enable us to set up clinical trials in children within the next two to three years. If our new treatment is successful, then boys with XLP won’t get infections anymore and they won’t get lymphoma. They will be able to live normal lives. We are not trying to make these children a little bit better. We are trying to cure them.”
1. XLP Research Trust, More information on XLP. http://www.xlpresearchtrust.org/default.asp Website accessed 6 November 2015.
|Professor H Bobby Gaspar MBBS MRCP MRCPCH PhD
|Dr Claire A Booth MBBS MRCPCH MSc PhD
|Molecular and Cellular Immunology Section, University College London Institute of Child Health
|20 July 2015
|Project start date
|15 February 2016
|Project end date
|1 October 2018