Breakthrough in ADA-SCID treatment: Gene therapy shows lasting immune restoration
Researchers have reported a landmark advance in treating ADA-SCID, a life-threatening genetic immune disorder. An experimental gene therapy developed by teams at UCLA, University College London (UCL), and Great Ormond Street Hospital (GOSH) restored and sustained immune system function in 59 of 62 children born with ADA-SCID, marking what the investigators describe as a durable and favorable safety profile.
ADA-SCID (adenosine deaminase deficiency–severe combined immunodeficiency) arises from mutations in the ADA gene that leaves the immune system unable to defend against infections. Infants and children with the condition face a high risk of life-threatening infections, and without treatment, many do not survive beyond the first two years of life. Conventional options—including bone marrow transplants from matched donors and weekly ADA enzyme injections—carry significant limitations and potential long-term risks.
How the therapy works
The approach uses a patient’s own blood stem cells, which generate all blood and immune cells. A modified lentivirus delivers a healthy copy of the ADA gene into these cells. The corrected stem cells are then infused back into the patient, where they begin producing functional immune cells that can fight infections. Immune reconstitution begins within weeks and typically reaches stable, normal levels after six to twelve months.
In the study published in the New England Journal of Medicine, senior author Dr. Donald Kohn (UCLA) and co-first authors Dr. Katelyn Masiuk and Dr. Claire Booth (GOSH) report long-term outcomes for children treated between 2012 and 2019. The results show durable immune function and a favorable safety profile over a total of 474 patient-years of follow-up, including patients treated more than a decade ago.
What the results mean for patients and families
Among the 62 treated children, 59 achieved successful and lasting immune recovery. Three children did not reach that milestone during the study period, but all were able to receive other standard therapies—two later received bone marrow transplants, and one continued ADA enzyme injections while preparing for a transplant. Most adverse events reported were mild or moderate and linked to preparatory procedures rather than the gene therapy itself.
“The durability of immune function, consistency over time, and continued safety are incredibly encouraging,” said Dr. Kohn. “This therapy has the potential to change the standard of care for ADA-SCID.”
Improving access through cryopreservation
More than half of treated children received a frozen (cryopreserved) preparation of corrected stem cells. The frozen approach yielded comparable outcomes to fresh cells, reducing the need for families to travel to specialized centers. Cryopreservation also enables better pre-treatment testing and more precise dosing of conditioning chemotherapy.
From research to potential regulation
With funding from the NIH, DHHS, California Institute for Regenerative Medicine, Orchard Therapeutics, and the UK NIHR GOSH Biomedical Research Centre, the UCLA team is pursuing regulatory steps toward FDA approval. A public-benefit company, Rarity PBC, is partnering to manufacture the therapy under pharmaceutical-grade standards after licensing the technology from UCLA.
“Our goal is FDA approval within two to three years, supported by strong clinical data and scalable manufacturing,” said Dr. Kohn.
The human story: Eliana’s journey
Eleven-year-old Eliana Nachem, diagnosed with ADA-SCID at 3 months, embodies the potential impact. After treatment at UCLA in 2014, she has attended public school, played basketball, and enjoyed a normal childhood years after a period of complete medical isolation. Her mother recalls the moment doctors described her daughter’s infusion as a “rebirth,” underscoring the therapy’s life-changing promise.
Why this matters
Beyond individual outcomes, this study represents the largest and longest follow-up of a gene therapy for ADA-SCID to date. If approved, the therapy could redefine treatment paradigms for genetic immune disorders and improve access through streamlined manufacturing and local collection, potentially benefiting patients worldwide.
Key takeaways
- Durable restoration of immune function in the majority of treated children (59/62).
- Long-term safety profile with mostly mild to moderate adverse events.
- Cryopreservation enables local collection and broader access.
- Active steps toward FDA approval and commercial-scale production.
As researchers continue to validate these findings and navigate regulatory pathways, families affected by ADA-SCID may soon have a safer, more accessible option to restore a fully functioning immune system.
