Overview: A new path for ADA-SCID treatment
Researchers from UCLA, University College London, and Great Ormond Street Hospital have reported a remarkable milestone in the fight against ADA-SCID, a rare and often fatal genetic immune disorder. In a long-term study published in the New England Journal of Medicine, an experimental gene therapy restored and sustained immune system function in 59 of 62 children treated between 2012 and 2019. The results, described as durable and stable beyond initial recovery, position this approach as a potentially transformative option for patients and families affected by ADA-SCID.
What is ADA-SCID and why this therapy matters
Severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) arises from mutations in the ADA gene, a critical enzyme for immune development. Without functional ADA, children face life-threatening infections with everyday activities such as attending school or playing with peers. If untreated, ADA-SCID can be fatal within the first two years of life. Standard treatments—bone marrow transplantation from a matched donor or weekly enzyme injections—can be effective for some, but they carry significant risks and do not always provide a lasting cure.
The science behind the breakthrough
The experimental therapy uses a patient’s own blood stem cells, which give rise to all immune and blood cells. A modified lentivirus delivers a healthy copy of the ADA gene into these cells, which are then reinfused into the patient. The corrected stem cells begin generating healthy immune cells, gradually rebuilding immune function. Immune reconstitution typically starts within weeks to months, but the complete restoration to normal function can take six to 12 months. Over the long term, the study shows that immune function remained stable in the majority of treated children, with a safety profile that did not reveal new treatment-related risks.
Long-term outcomes and safety
With 474 total patient-years of follow-up, this is the largest and longest look at a gene therapy of this kind. Among those treated, only three did not achieve lasting immune restoration, and two of these ultimately received a bone marrow transplant while one remained on enzyme therapy during preparatory phases. Importantly, most adverse events were linked to routine preparatory procedures rather than the gene therapy itself, underscoring a favorable safety signal for a pediatric population with critical needs.
Accessibility and manufacturing advances
A key innovation in this program is the feasibility of cryopreserved (frozen) stem cell products. More than half of treated children received frozen cells, which yielded comparable outcomes to fresh cells. This freezing method enables local collection with centralized processing and distribution, reducing travel burdens for families and enabling more precise dosing and quality control prior to infusion. As a result, the therapy could become more widely accessible to patients around the world, particularly those far from specialized centers.
Path to regulatory approval and patient impact
The UCLA team, with funding from NIH, the California Institute for Regenerative Medicine, and UK partners, is pursuing FDA approval. The goal is to bring this therapy to market within the next two to three years, assuming scalable manufacturing can meet rigorous pharmaceutical standards. The program’s success is also illustrated by individual stories, such as Eliana Nachem, an 11-year-old who has lived a normal life since treatment and now enjoys school, sports, and independence she could not imagine as an infant with ADA-SCID.
Eliana’s story: a life transformed
Diagnosed at three months old, Eliana’s early life involved isolation and careful conditioning to minimize infections. After receiving the corrected cells in 2014, her immune system gradually recovered, and she returned to ordinary childhood activities. Her mother describes the moment of treatment as a rebirth, a sentiment echoed by families who see their children grow into typical, carefree lives. While not every case is identical, the overall trajectory reported in the study offers renewed optimism for children with ADA-SCID and their communities.
What’s next
As researchers push toward regulatory approval, the broader implications of this work extend beyond ADA-SCID. The approach—using a patient’s own stem cells to deliver a functional gene—could inform therapies for other genetic immune disorders and blood diseases. The continued emphasis is on durable immune restoration, long-term safety, and the practical steps needed to deliver a treatment that can be manufactured at scale for patients nationwide and worldwide.
