Updated on
What did the project achieve?
Deficiency of adenosine deaminase 2 (DADA2) is a rare genetic condition that causes strokes, heart attacks, severe skin ulcers, a weakened immune system and bone marrow failure. Currently, there is no cure and, although treatments exist to help manage symptoms, they are not always effective and can sometimes cause serious side effects.
“Our laboratory research brings us closer to a curative treatment for children with DADA2,” says Professor Despina Eletheriou of UCL Great Ormond Street Institute of Child Health. “If successful, this could ultimately transform the lives of children with this debilitating condition worldwide – and open the door for similar treatments for children with other inherited inflammatory illnesses in the future.”
Professor Eletheriou’s team is developing a pioneering new gene therapy for DADA2. The therapeutic approach involves collecting a patient’s blood stem cells and using a harmless virus to introduce a healthy copy of the ADA2 gene – the gene that is faulty in DADA2 – before transplanting these corrected cells back into the body.
“In laboratory experiments, we’ve now established a safe and reliable way to genetically correct blood stem cells from patients with DADA2,” says Professor Eletheriou. “We’ve also shown we can successfully correct the underlying immune system problems that drive the disease.”
Building on these promising results, the researchers are now continuing their laboratory studies – including experiments to establish the safety and effectiveness of this treatment approach in a laboratory model, bringing it closer to clinical application.
“As a result of this project, we’ve secured additional funding to complete the remaining laboratory studies required before we can take the next step and begin a clinical trial of this new gene therapy,” says Professor Eletheriou. “We now have a unique opportunity to work towards a complete cure for DADA2 – one that could free patients from the lifelong burden of this disease.”
The team hopes to launch a clinical trial of their gene therapy for DADA2 within the next two to three years.
This research was completed on
How are children’s lives affected now?
Deficiency of adenosine deaminase 2 (DADA2) is a rare inherited type of vasculitis. A child’s immune system mistakenly attacks their blood vessels, causing them to swell and narrow – and leads to continuous inflammation that can damage tissues and organs.
“While the first symptoms may be mild, a child may go on to develop more serious complications including repeated strokes, problems affecting the immune system, gut perforation and severe skin ulceration,” says Professor Eleftheriou.
DADA2 is caused by faults in a gene that helps to make an enzyme called ADA2, which plays an important role in supporting the lining of blood vessels – and in white blood cell development. Currently, there is no cure for the condition – but treatments are available that can help to reduce symptoms.
“Current treatments include drugs that can damp down the immune system – or, for some children, a bone marrow transplant,” says Professor Eleftheriou. “But these are not always effective and can sometimes have serious side effects.”
How could this research help?
“Our goal is to develop gene therapy as a safe and effective new treatment for children with DADA2,” says Professor Eleftheriou.
The approach involves taking blood stem cells (immature cells that can develop into all types of blood cells) from the patient, introducing a working copy of the ADA2 gene – and then transplanting them back into the patient’s body.
“Building on encouraging results from previous experiments, we will first investigate the best way of getting the gene into patient blood stem cells in the laboratory,” says Professor Eleftheriou.
The researchers will then transplant treated blood stem cells into a laboratory model and evaluate the effects on the body.
“We hope our results will guide the development of an international programme of research into gene therapy for children with DADA2.” says Professor Eleftheriou.
If the approach is successful for this condition, it could ultimately lead to the development of similar treatments for children with other inherited inflammatory diseases.
Research table
Project details
| Project Leader | Professor Despina Eleftheriou, MB BS MRPCH PhD |
| Location | Department of Infection, Inflammation and Rheumatology, UCL Great Ormond Street Institute of Child Health |
| Project Team |
Professor Paul A Brogan, MB ChB MSc BSc FRCPCH PhD
Dr Ying Hong, BSc MSc PhD Professor Adrian Thrasher, MB PhD FMedSci PhD Professor Helen Lachmann, MB BS MD Professor Philip Hawkins, PhD FMedSci Dr Ebun Omoyinmi, PhD |
| Other Locations |
Department of Molecular Immunology, UCL Great Ormond Street Institute of Child Health
National Amyloidosis Centre, UCL Royal Free Hospital Campus, University College London |
| Grant Amount | £177,915 |
| Start Date | |
| End Date | |
| Duration | 24 months |
| Grant Code (GN number) | GN2864 |
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