An experimental gene therapy developed by researchers at UCLA, University College London, and Great Ormond Street Hospital has restored and maintained immune system function in 59 out of 62 children diagnosed with ADA-SCID, a rare genetic immune disorder. ADA-SCID, or severe combined immunodeficiency due to adenosine deaminase deficiency, is caused by mutations in the ADA gene, which is necessary for immune function. Without treatment, children with ADA-SCID are at risk of life-threatening infections and often do not survive past the age of two.
Traditional treatments for ADA-SCID include bone marrow transplants from matched donors or weekly enzyme injections, both of which have limitations and potential long-term risks. The new gene therapy approach involves collecting a child’s blood stem cells, modifying them with a lentivirus to deliver a healthy ADA gene, and reinfusing them into the patient. The corrected stem cells then produce healthy immune cells, though it takes six to twelve months for the immune system to fully recover.
The findings, published in the New England Journal of Medicine, are based on long-term outcomes for children treated between 2012 and 2019. Dr. Donald Kohn of UCLA, the study’s senior author, said, “These results are what we hoped for when we first began developing this approach. The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging.”
The study is the largest and longest follow-up of this type of gene therapy, covering 474 patient-years, including five patients treated more than a decade ago. For the 59 successfully treated patients, immune function has remained stable beyond the initial recovery period, and no treatment-limiting complications have been reported. Dr. Kohn noted, “What’s most remarkable is that everything has been completely stable beyond the initial three-to-six-month recovery period.” Most adverse events were mild or moderate and related to preparatory procedures rather than the therapy itself.
Three patients did not respond to the therapy, but all were able to return to standard treatments. Two received bone marrow transplants, and one was preparing for a transplant while receiving enzyme injections.
A significant portion of the children received a frozen preparation of the corrected stem cells, which proved as effective as using fresh cells. Dr. Katelyn Masiuk, co-first author, explained, “The freezing approach allows children with ADA-SCID to have their stem cells collected locally, then processed at a manufacturing facility elsewhere and shipped back to a hospital near them. This removes the need for patients and their families to travel long distances to specialist centers.” The method also allows for better testing and quality control before treatment.
With support from the California Institute for Regenerative Medicine, the UCLA team is working to apply for FDA approval. Rarity PBC has licensed the therapy from UCLA and is partnering with commercial manufacturers. Dr. Kohn stated, “Our goal is to have this therapy FDA-approved within two to three years. The clinical data strongly supports approval — now we need to demonstrate that we can manufacture the treatment under commercial pharmaceutical standards.”
One patient, Eliana Nachem, received the therapy as an infant in 2014. Her mother, Caroline, described their experience: “The data was absolutely stunning — like a bouquet of flowers over the phone. Almost overnight, we knew we had to do this.” Eliana’s recovery allowed her to attend school and participate in normal activities. Caroline added, “I am eternally grateful to every single scientist, doctor, lab worker, nurse, hospital security guard — all the people who had anything to do with this gene therapy coming into existence and saving her.”
The research received funding from the National Institutes of Health, the U.S. Department of Health & Human Services, the California Institute for Regenerative Medicine, Orchard Therapeutics, and the U.K. National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre.
