Gene Therapy Restores Immune Function in Children with Rare Genetic Disorder
A gene therapy developed to treat severe leukocyte adhesion deficiency-I (LAD-I), a rare immune disorder affecting about one in a million people, has shown sustained clinical benefit in all nine children treated during a multi-center international trial co-led by UCLA. The therapy corrected the underlying genetic defect in each child, enabling them to fight infections and live symptom-free for at least two years after treatment.
LAD-I is caused by mutations in the gene encoding CD18, a protein necessary for white blood cells to exit the bloodstream and respond to infections. Without functional CD18, children with severe LAD-I suffer from frequent and dangerous infections, and most do not survive past early childhood without intervention.
Results from the trial were published in The New England Journal of Medicine. The study included patients ranging from 5 months to 9 years old who were treated at UCLA Mattel Children’s Hospital, Great Ormond Street Hospital in London, and Hospital Infantil Universitario Niño Jesús in Madrid. Each child showed immune reconstitution and resolution of symptoms, including skin lesions and inflamed gums, and has remained free of serious infections.
“These children are no longer defined by their diagnosis,” said Donald Kohn, senior author of the study and professor at UCLA. “Seeing them healthy and thriving without serious infections, without frequent hospital visits, is a testament to how consistently beneficial this therapy is.”
The therapy, developed by Rocket Pharmaceuticals, uses a lentiviral vector to deliver a working copy of the CD18 gene into patients’ blood stem cells. These genetically modified cells are then reinfused, where they give rise to immune cells capable of responding to infections. This approach allows patients to serve as their own stem cell donors, avoiding the risks of traditional bone marrow transplants, such as graft-versus-host disease.
All nine children achieved normalized CD18 protein expression and white blood cell function. No severe adverse events linked to the therapy were reported, and none experienced graft failure or immune complications. Six of the nine participants have now enrolled in a 15-year follow-up study at UCLA to monitor the therapy’s long-term safety and durability.
“This therapy presents a new path forward in treating these rare immune conditions and reducing the burdens and risks for patients,” said Claire Booth, a consultant in pediatric immunology and gene therapy at Great Ormond Street Hospital and a co-lead author on the study.
Among those treated were three siblings—Ava, Olivia, and Landon Langenhop—who received the therapy at UCLA. Their parents described a dramatic shift in daily life after years of hospital visits and constant infection-related fears. While they struggled for years, the kids are now living normal lives. This gene therapy is currently under review by the U.S. Food and Drug Administration, but these initial results are promising for other individuals with this condition.
Publication Details
Booth, C., Sevilla, J., Almarza, E., Kuo, C. Y., Zubicaray, J., Terrazas, D., ... Kohn, D. B. (2025). Lentiviral gene therapy for severe leukocyte adhesion deficiency type 1. New England Journal of Medicine, 392(17), 1698–1709. https://doi.org/10.1056/NEJMoa2407376
A gene therapy developed to treat severe leukocyte adhesion deficiency-I (LAD-I), a rare immune disorder affecting about one in a million people, has shown sustained clinical benefit in all nine children treated during a multi-center international trial co-led by UCLA. The therapy corrected the underlying genetic defect in each child, enabling them to fight infections and live symptom-free for at least two years after treatment.
LAD-I is caused by mutations in the gene encoding CD18, a protein necessary for white blood cells to exit the bloodstream and respond to infections. Without functional CD18, children with severe LAD-I suffer from frequent and dangerous infections, and most do not survive past early childhood without intervention.
Results from the trial were published in The New England Journal of Medicine. The study included patients ranging from 5 months to 9 years old who were treated at UCLA Mattel Children’s Hospital, Great Ormond Street Hospital in London, and Hospital Infantil Universitario Niño Jesús in Madrid. Each child showed immune reconstitution and resolution of symptoms, including skin lesions and inflamed gums, and has remained free of serious infections.
“These children are no longer defined by their diagnosis,” said Donald Kohn, senior author of the study and professor at UCLA. “Seeing them healthy and thriving without serious infections, without frequent hospital visits, is a testament to how consistently beneficial this therapy is.”
The therapy, developed by Rocket Pharmaceuticals, uses a lentiviral vector to deliver a working copy of the CD18 gene into patients’ blood stem cells. These genetically modified cells are then reinfused, where they give rise to immune cells capable of responding to infections. This approach allows patients to serve as their own stem cell donors, avoiding the risks of traditional bone marrow transplants, such as graft-versus-host disease.
All nine children achieved normalized CD18 protein expression and white blood cell function. No severe adverse events linked to the therapy were reported, and none experienced graft failure or immune complications. Six of the nine participants have now enrolled in a 15-year follow-up study at UCLA to monitor the therapy’s long-term safety and durability.
“This therapy presents a new path forward in treating these rare immune conditions and reducing the burdens and risks for patients,” said Claire Booth, a consultant in pediatric immunology and gene therapy at Great Ormond Street Hospital and a co-lead author on the study.
Among those treated were three siblings—Ava, Olivia, and Landon Langenhop—who received the therapy at UCLA. Their parents described a dramatic shift in daily life after years of hospital visits and constant infection-related fears. While they struggled for years, the kids are now living normal lives. This gene therapy is currently under review by the U.S. Food and Drug Administration, but these initial results are promising for other individuals with this condition.
Publication Details
Booth, C., Sevilla, J., Almarza, E., Kuo, C. Y., Zubicaray, J., Terrazas, D., ... Kohn, D. B. (2025). Lentiviral gene therapy for severe leukocyte adhesion deficiency type 1. New England Journal of Medicine, 392(17), 1698–1709. https://doi.org/10.1056/NEJMoa2407376