An experimental gene therapy has demonstrated sustained immune system restoration in children diagnosed with ADA-SCID, a rare genetic disorder that severely compromises the immune system. The therapy, developed by researchers at UCLA, University College London, and Great Ormond Street Hospital, was tested in 62 children, with 59 showing long-term immune function recovery, according to a study published in the New England Journal of Medicine.
ADA-SCID, or severe combined immunodeficiency due to adenosine deaminase deficiency, is caused by mutations in the ADA gene. Children with this condition are highly vulnerable to infections and face life-threatening risks from everyday activities. If left untreated, the disorder is often fatal within the first two years of life. Current standard treatments include bone marrow transplants from matched donors or weekly enzyme injections, both of which have limitations and potential risks.
The gene therapy involves collecting a child’s blood stem cells, using a modified lentivirus to insert a healthy ADA gene, and then reinfusing the corrected cells into the patient. This process enables the production of functional immune cells. The full reconstitution of the immune system typically occurs within six to twelve months after treatment.
“These results are what we hoped for when we first began developing this approach,” said Dr. Donald Kohn, a distinguished professor at UCLA and senior author of the study. “The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging.”
The study represents the largest and longest follow-up for gene therapy of this kind, covering 474 patient-years of data. Of the three children for whom the therapy was not successful, two received bone marrow transplants, and one continued with enzyme therapy while preparing for a transplant.
“What’s most remarkable is that everything has been completely stable beyond the initial three-to-six-month recovery period,” Kohn said. He added that most adverse events were mild or moderate and related to preparatory procedures rather than the gene therapy itself.
Another significant development was the use of cryopreserved (frozen) corrected stem cells, which yielded similar outcomes to fresh cells. This method allows stem cells to be collected locally, processed at specialized facilities, and shipped back to hospitals near the patients. “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,” said Dr. Katelyn Masiuk, co-first author of the study.
The research was funded by 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.
The UCLA team is working toward securing FDA approval for the therapy. “Our goal is to have this therapy FDA-approved within two to three years,” Kohn said. “The clinical data strongly supports approval — now we need to demonstrate that we can manufacture the treatment under commercial pharmaceutical standards.”
The therapy’s impact is illustrated by the story of Eliana Nachem, who was diagnosed with ADA-SCID as an infant. After receiving the gene therapy at UCLA, Eliana’s immune system recovered, allowing her to attend school and participate in normal activities. Her mother, Caroline, said, “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.”
