Groundbreaking long-term results for ADA-SCID gene therapy
A multinational team led by Great Ormond Street Hospital (GOSH), University College London (UCL), and the University of California, Los Angeles (UCLA) has reported the longest follow-up to date for children treated with a gene therapy for ADA-SCID, a rare immune deficiency. The study, published in the New England Journal of Medicine, follows a cohort treated between 2012 and 2019 and documents remarkable long-term safety and efficacy of this ex vivo lentiviral gene therapy.
What is ADA-SCID and why this therapy matters
ADA-SCID, or adenosine deaminase deficient severe combined immunodeficiency, is a life-threatening genetic disorder that leaves children without a functional immune system. Without treatment, many affected infants cannot survive beyond the early years of life due to severe infections. Previously, care-intensive therapies—enzyme-replacement, immunoglobulin infusions, and frequent antibiotics—were used while doctors searched for a bone marrow donor. The advent of lentiviral gene therapy offers a potential cure by correcting the faulty blood stem cells outside the body and returning them to the patient.
Study design and key findings
The analysis tracked 62 children treated across the UK and the USA, with follow-up averaging 7.5 years. This makes it the largest cohort of children receiving the standard ex vivo gene therapy to date. The results are striking:
- 100% survival among treated children.
- About 95% (59 of 62) achieved cure, with immune systems that function well enough to respond to routine childhood vaccines.
- Responders were able to discontinue enzyme-replacement therapy within six months of treatment.
- There were no serious treatment-related complications, and non-responders could pursue bone marrow transplantation as needed.
The data reinforce that lentiviral gene therapy can deliver durable immune reconstitution with a favorable safety profile, supporting its role as a standard-of-care option for ADA-SCID in children.
Implications for future care and policy
Professor Claire Booth, a leading investigator from GOSH and UCL, noted that nearly all treated patients achieved cure and could lead normal lives, including access to vaccines. The study’s durability—from early success to long-term follow-up—also provides reassurance to clinicians and families considering gene therapy for other rare diseases treated with the same technology.
Real-world impact: patient stories and broader access
One participant, Andy Cash from Portlaoise, Ireland, illustrates the journey. Diagnosed as a newborn, Andy faced a life-threatening immunodeficiency and severe infection risk. After gene therapy at GOSH, his mother Mary describes a markedly improved quality of life, with Andy thriving, participating in school activities, and engaging in sports. Stories like Andy’s highlight how long-term success translates into tangible daily improvements for children and families.
Looking ahead: regulatory and access considerations
In 2024, GOSH announced plans, supported by charity partners, to explore whether the hospital could secure market authorization for this ADA-SCID gene therapy in the UK, improving access for eligible patients. Rare-disease therapies often struggle to find commercial viability, so evidence from this cohort is crucial for policy discussions about funding and distribution.
Conclusion
With 100% survival and a cure rate near 95%, this long-term study marks a pivotal moment for ADA-SCID and ex vivo lentiviral gene therapy. It demonstrates enduring safety and efficacy, providing hope for children with this rare immunodeficiency and reinforcing the potential of gene therapies to transform lives in the long run.
Support for the research came from NIHR GOSH BRC and other partners, underscoring the collaborative effort that makes these advances possible. As researchers continue to build on these results, the field moves closer to making gene therapy a reliable, long-lasting option for rare diseases worldwide.
