Breakthrough in pediatric ADA-SCID treatment
A large international study led by researchers from Great Ormond Street Hospital (GOSH), University College London (UCL), and the University of California, Los Angeles (UCLA) has demonstrated the long-term safety and effectiveness of a standard lentiviral gene therapy for ADA-SCID, a rare and life-threatening immune disorder. The cohort, followed for an average of 7.5 years, shows a remarkable rate of survival and cure, reinforcing the therapy as a durable option for children with this condition.
Understanding ADA-SCID and the therapy
ADA-SCID (adenosine deaminase deficient severe combined immunodeficiency) is caused by mutations in the gene responsible for producing the enzyme adenosine deaminase, crucial for a functioning immune system. Without a properly working immune system, affected children are highly susceptible to infections and may not live past early childhood if untreated. Newborn screening for SCID is expanding in several countries to enable earlier detection and intervention.
Traditionally, treatment involved lifelong enzyme-replacement therapy, immunoglobulin infusions, and preventive antibiotics until a suitable bone marrow donor could be found. The gene therapy studied here uses lentiviral vectors to modify a patient’s own hematopoietic stem cells ex vivo, correcting the genetic defect, and then returning the cells to the patient. This approach aims to provide a lasting, self-sustaining source of healthy immune cells.
The study results: durability and safety
The international trial enrolled 62 patients treated between 2012 and 2019 in the UK and the USA. On average, participants were tracked for 7.5 years, with five individuals followed for more than a decade, making this the largest cohort of children treated with this ex vivo stem cell gene therapy to date.
Key findings include a 100% survival rate among treated children and a 95% cure rate. Responders stopped enzyme-replacement therapy within six months and achieved robust responses to routine childhood vaccinations, such as tetanus, measles, mumps, and rubella (MMR). Importantly, none of the treated children experienced serious adverse events related to the therapy, and those who did not fully respond to the gene therapy proceeded to a bone marrow transplant as a fallback option.
Implications for the field and patients
These results provide strong long-term evidence that lentiviral gene therapy is a safe and effective cure for ADA-SCID in children, with durable immune reconstitution and normal vaccination responses. The data bolster confidence in extending this technology to other genetic conditions treated with the same ex vivo approach and support ongoing development of market access pathways for this therapy in the UK and beyond.
GOSH researchers, led by Professor Claire Booth, emphasize the significance of patient and family participation in trial success. The study’s scale and multiyear follow-up strengthen the case for broader adoption and continued investment in gene and cell therapy facilities.
Real-world impact: a patient story
One participant, Andy from Portlaoise, Ireland, was diagnosed with ADA-SCID as a newborn. His family faced isolation and limited donor options before joining the trial. Andy received gene therapy at GOSH and has since thrived, now enjoying school, sports, and an active social life that previously would have been impossible. His mother Mary describes a life-changing outcome and a hopeful future for other families facing ADA-SCID.
Looking ahead: access and affordability
In 2024, GOSH announced plans, with support from NIHR GOSH BRC and partners, to explore market authorization for ADA-SCID gene therapy in the UK. Establishing licensing could make this curative treatment more accessible to children and young people with rare diseases, addressing a core challenge in developing therapies for small patient populations.
Conclusion
The study marks a milestone in gene therapy for inherited immunodeficiencies, underscoring the durability and safety of lentiviral approaches. As centers like GOSH continue to refine manufacturing and clinical pathways, families affected by ADA-SCID can look forward to real options for sustained immune health and normal development.
