N Engl J Med

Experimental gene therapy safe, effective in children with rare immune disorder

October 21, 2025

Study details: This long-term follow-up study evaluated 62 patients with adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID) treated between 2012 and 2019 in the U.S. and U.K. Patients received autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding human ADA following nonmyeloablative busulfan conditioning. Median follow-up was 7.5 years, totaling 474 patient-years. Primary endpoints were overall and event-free survival; secondary endpoints included immune reconstitution and safety.

Results: Overall survival was 100%, and event-free survival was 95% (59/62 patients). All patients with successful engraftment maintained stable gene marking, ADA activity, metabolic detoxification, and robust immune recovery. Nearly all (98%) discontinued immunoglobulin replacement and demonstrated protective vaccine responses. No leukoproliferative events, clonal dominance, or replication-competent lentivirus were detected. Late adverse events were rare and unrelated to the gene therapy.

Clinical impact: These findings confirm lentiviral gene therapy as a safe, effective, and potentially curative treatment for ADA-SCID, eliminating the need for lifelong enzyme replacement and avoiding risks of allogeneic transplantation.

Source:

Booth C, et al. (2025, October 16). N Engl J Med. Long-Term Safety and Efficacy of Gene Therapy for Adenosine Deaminase Deficiency. https://pubmed.ncbi.nlm.nih.gov/41092330/