An experimental gene therapy has shown long-term success in restoring immune function in children with ADA-SCID, a rare genetic immune disorder, according to a study published in the New England Journal of Medicine. The therapy, developed by researchers at UCLA, University College London, and Great Ormond Street Hospital, was tested on 62 children between 2012 and 2019. Of these, 59 maintained healthy immune systems following treatment.
ADA-SCID, or severe combined immunodeficiency due to adenosine deaminase deficiency, is caused by mutations in the ADA gene. This condition leaves children highly vulnerable to infections and can be fatal within two years if untreated. Standard treatments include bone marrow transplants or weekly enzyme injections, but both options have limitations and potential long-term risks.
The gene therapy approach involves collecting a child’s blood stem cells and using a modified lentivirus to insert a healthy ADA gene. The corrected cells are then infused back into the patient, where they begin producing healthy immune cells. Full immune system recovery takes six to twelve months.
“These results are what we hoped for when we first began developing this approach,” said Dr. Donald Kohn of UCLA. “The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging.”
The study followed patients for a total of 474 patient-years, including five children who received the therapy more than ten years ago. Most adverse events were mild or moderate and linked to preparatory procedures rather than the gene therapy itself. Three children did not respond to the treatment but were able to return to standard therapies.
“What’s most remarkable is that everything has been completely stable beyond the initial three-to-six-month recovery period,” Kohn said. “Treatment was successful in all but three of the 62 cases, and all of those children were able to return to current standard-of-care therapies.”
A notable aspect of the study was the use of cryopreserved (frozen) corrected stem cells for more than half of the children. Outcomes were similar to those who received fresh cells. Dr. Katelyn Masiuk noted that this method allows for local collection and remote processing of cells, making the therapy more accessible and reducing the need for families to travel long distances.
“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,” Masiuk said. “This removes the need for patients and their families to travel long distances to specialist centers.”
The research was funded by several organizations including the National Institutes of Health and the California Institute for Regenerative Medicine. With continued support, the UCLA team aims to apply for FDA approval within two to three years. Rarity PBC has licensed the therapy and is working with manufacturing partners to meet pharmaceutical standards.
“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 study also shared the story of Eliana Nachem from Virginia, who received the therapy as an infant and now lives a normal life. Her mother expressed gratitude for everyone involved in developing the treatment: “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.”
