Groundbreaking Study Highlights Long-Term Success of ADA-SCID Gene Therapy
A landmark international study led by researchers from Great Ormond Street Hospital (GOSH), University College London (UCL), and the University of California, Los Angeles (UCLA) shows that gene therapy can provide durable, life-changing results for children with ADA-SCID, a rare and life-threatening immune deficiency. The team followed 62 children who received ex vivo lentiviral gene therapy between 2012 and 2019 for an average of 7.5 years, making this the largest long-term cohort to date for this treatment approach.
What is ADA-SCID?
ADA-SCID stands for adenosine deaminase deficient severe combined immunodeficiency. It is caused by mutations in the gene that produces the enzyme adenosine deaminase, which is essential for a functioning immune system. Without a working ADA enzyme, children have severely compromised immunity and face life-threatening infections early in life. In some countries, newborn screening now helps detect the condition sooner, giving families hope for effective treatment.
How the Gene Therapy Works
The therapy uses an ex vivo approach: a patient’s own blood or bone marrow cells are collected, modified in the laboratory with a lentiviral vector to fix the genetic defect, and then returned to the patient. The goal is to reconstitute a healthy immune system without the need for a donor bone marrow transplant.
Key Findings from the 7.5-Year Follow-Up
Among the treated cohort, 100% survived the procedure, and 95% (59 of 62) achieved a cure. Those who responded to the treatment stopped enzyme-replacement therapy within six months and could mount normal responses to routine vaccines such as tetanus and MMR. Importantly, there were no widespread serious complications, and nonresponders were able to receive bone marrow transplants when needed. Five children were followed for more than a decade, underscoring the durability of lentiviral gene therapy.
Impact on Daily Life
Previously, ADA-SCID patients relied on ongoing enzyme-replacement therapy, immunoglobulin infusions, antibiotics, and, when possible, a bone marrow donor. The new data show that treated children can lead typical childhoods, attend school, and participate in vaccinations—milestones all but unreachable before successful gene therapy.
Clinical Significance and Future Prospects
The study confirms lentiviral gene therapy as the standard ex vivo option for ADA-SCID and provides robust long-term safety and efficacy data. Lead researchers emphasize that these results bolster confidence in applying similar gene-editing strategies to other rare immune disorders. The findings also support ongoing discussions about market authorization to improve patient access, particularly in the UK, where GOSH aims to streamline treatment access for children and young people with ADA-SCID.
Personal Stories: Andy’s Journey
One participant, Andy from Ireland, was diagnosed just weeks after birth and faced isolation and frequent infections. After gene therapy treatment at GOSH, he has thrived, joining a boxing club and enjoying school with his siblings. His experience illustrates how durable immune reconstitution can transform a child’s life and family dynamics.
Looking Ahead
With support from NIHR GOSH Biomedical Research Centre and collaborators, researchers aim to expand access and explore market authorization for this therapy. The ongoing success of ADA-SCID treatment also fuels efforts to adapt ex vivo gene therapies to other rare conditions, offering hope for a broader patient population.
As the ADA-SCID story demonstrates, combining sustained scientific innovation with patient-centered care can redefine what is possible in pediatric immunology—and set a benchmark for long-term outcomes in gene therapy.
