Groundbreaking therapy offers durable immune restoration for ADA-SCID
An experimental gene therapy developed by researchers at UCLA, University College London (UCL) and Great Ormond Street Hospital (GOSH) has achieved durable restoration of immune system function in 59 of 62 children born with ADA-SCID, a rare and often deadly genetic immune disorder. The long-term follow-up results, published in the New England Journal of Medicine, mark a significant milestone in the treatment of severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).
What is ADA-SCID and why this therapy matters
ADA-SCID arises from mutations in the ADA gene, which impairs the production of an enzyme critical for immune cell development. Without effective immune defenses, even ordinary childhood activities—going to school, meeting friends, or playing—can expose children to life-threatening infections. If left untreated, the condition can be fatal within the first two years of life. Traditional treatments, such as bone marrow transplants from matched donors or weekly enzyme injections, are lifesaving for some but carry substantial limitations and potential long-term risks.
The therapy: how it works
The therapy begins with a child’s own blood stem cells, which generate all immune cells. Researchers remove these cells, use a modified lentivirus to insert a healthy copy of the ADA gene, and then re-infuse the corrected cells back into the patient. The idea is to reconstitute a functional immune system from the child’s own corrected cells, reducing reliance on donor matching and lifelong enzyme therapy.
Immune reconstitution begins relatively quickly after reinfusion, but it typically takes six to twelve months for the immune system to reach normal levels. The study notes that subsequent infections decline as the immune apparatus stabilizes, with most adverse events tied to preparative conditioning rather than the gene therapy itself.
Long-term outcomes: durability and safety
The study tracked 474 total patient-years of follow-up, including five patients treated more than a decade ago. Among the 59 patients who achieved immune restoration, immune function has remained stable beyond the initial recovery period, with no treatment-limiting complications reported. Senior author Dr. Donald Kohn of UCLA emphasized the durability and safety observed: “What’s most remarkable is that everything has been completely stable beyond the initial three-to-six-month recovery period.”
While three of the original 62 treated patients did not achieve durable immune restoration, they nonetheless transitioned back to standard-of-care therapies: two underwent bone marrow transplants, and one continued ADA enzyme injections while preparing for a transplant at data cutoff.
Expanding access: cryopreservation and global reach
A key advancement in this work is the successful use of frozen (cryopreserved) corrected stem cells. More than half of treated children received a frozen product, with outcomes comparable to those who received fresh cells. This freezing approach enables local cell collection, centralized manufacturing, and shipping back to the patient’s hospital, reducing the demand for travel to specialized centers. It also allows for more robust quality control and precise dosing of the conditioning chemotherapy used before therapy.
Path to wider availability: FDA consideration and manufacturing readiness
With funding from the California Institute for Regenerative Medicine, UCLA researchers are pursuing the steps needed for FDA approval. The therapy has been licensed to a public benefit company, and partnerships with commercial manufacturers aim to produce the treatment under pharmaceutical-grade conditions. The team’s goal is to achieve FDA approval within two to three years, contingent on demonstrating scalable, safe manufacturing alongside solid clinical data.
Real lives, real impact: Eliana’s story
An illustrative example is Eliana Nachem, an 11-year-old from Virginia who was diagnosed with ADA-SCID at three months old. Isolation, aggressive infection prevention, and a limited childhood seemed to be Eliana’s fate until she received her corrected cells at UCLA in 2014. Her mother recalls a profound moment when doctors described the infusion as a “rebirth” for their daughter. Ten years later, Eliana attends public school, plays basketball, and enjoys a normal childhood—testimony to the therapy’s potential to restore not just immune function but everyday hope.
Why this matters for families and the field
The ADA-SCID gene therapy represents a turning point, potentially offering one-time treatment with lasting immune protection and reducing the risks associated with donor transplants and ongoing enzyme replacement. The collaborative effort—spanning the United States and the United Kingdom—highlights the power of international collaboration in tackling rare diseases. As researchers push toward regulatory approval, the focus remains on safety, manufacturing quality, and equitable access for patients worldwide.
