Key takeaways
- Severe leukocyte adhesion deficiency-I is a rare genetic disease that prevents white blood cells from functioning normally, leaving affected children susceptible to recurrent, life-threatening infections.
- In a UCLA clinical trial, Dr. Donald Kohn treated young patients using a gene therapy that adds a healthy copy of the gene to the patients' own blood stem cells.
- The therapy, now approved by the FDA under the accelerated approval pathway, could provide a blueprint for developing and commercializing therapies for other rare diseases.
Dr. Donald Kohn has been developing gene therapies for rare pediatric immune disorders for over 30 years. Today, his role in a clinical trial has culminated in the first-ever U.S. Food and Drug Administration-approved therapy for severe leukocyte adhesion deficiency-I — a genetic condition characterized by recurrent infections and, often, early death.
The rare pediatric disease affects approximately one in one million children globally. Mutations in the ITGB2 gene disrupt the normal function of two proteins — CD11 and CD18 — that work together to help white blood cells reach and respond to infections. When this process breaks down, children become susceptible to recurrent, life-threatening bacterial and fungal infections. Without treatment, survival beyond childhood is rare.
Approval of the therapy, marketed under the name Kresladi, was based on the results of a clinical trial led at UCLA by Kohn, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.
In an April 2025 study in the New England Journal of Medicine, Kohn detailed two-year outcomes from the phase 1-2 trial, reporting on the sustained efficacy and safety of the therapy for all patients treated. All patients showed sustained immune reconstitution following treatment, with immune function approaching levels seen in children without the disease.
"I saw a marked improvement across all patients in terms of restored immune function," said Kohn, who is also a distinguished professor of microbiology, immunology and molecular genetics in the UCLA College and of pediatrics and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA. "Seeing these patients annually for their follow-up visits and witnessing that they no longer battle life-threatening infections has been incredibly meaningful."
Investigators enrolled nine patients aged 5 months to 9 years with severe LAD-I from across the globe. The small cohort reflects the rarity of the condition. Of the nine patients, the UCLA team enrolled and treated six; three were treated in London and Spain.
The clinical trial was conducted through a collaboration between UCLA investigators and Rocket Pharmaceuticals, which sponsored the study.
A gene therapy using patients' own cells
The one-time gene therapy works by adding in a healthy copy of the ITGB2 gene to each child's blood stem cells, then returning these cells to that child, enabling their bodies to produce functional immune cells to fight infections and heal wounds more quickly. By using patients' own cells, the therapy circumvents the risk of immune system rejection associated with donor cells, or graft-versus-host disease.
"We've found that for the patients we've treated, this therapy is associated with fewer short- and long-term toxicities than those often associated with bone marrow transplantation, which requires a lot more chemotherapy and immunosuppressive drugs before and after the transplant," Kohn said.
All nine trial patients survived without needing a bone marrow transplant, and no instances of graft failure or immune rejection were reported. Importantly, data showed a significant reduction in severe infections that required hospital stays.
The children's pre-treatment high white blood cell counts, or leukocytosis, improved consistently, and researchers observed sustained presence of the therapeutic gene and an increase in CD18 and CD11a expression, which is critical to immune system function.
From decades of research to FDA approval
Today's news marks a major milestone for Kohn, who has spent over three decades developing and testing gene therapies for immune diseases. Kresladi will be the first of these therapies that Kohn has been involved in to receive FDA approval — a critical step in ensuring that the therapy can reach the patients who need it.
Developed by Rocket Pharmaceuticals, the therapy is expected to become available through specialized treatment centers experienced in ex vivo gene therapy procedures. Confirmation of clinical benefit will be based on the evaluation of longer-term follow-up data of treated patients in the clinical study and through a post-marketing registry.
The approval is also a significant win for the California Institute for Regenerative Medicine, or CIRM, a California state agency that funds stem cell and gene therapy research. Established in 2004 to accelerate stem cell therapies, CIRM co-funded clinical trials for the gene therapy in collaboration with Rocket and is now celebrating the first-ever FDA approval made possible through its support.
Kohn is optimistic that this approval will encourage more companies to develop treatments for other rare diseases. He is conducting clinical trials to test a treatment for another deadly immune system disorder known as ADA-SCID, or adenosine deaminase–deficient severe combined immunodeficiency. The results are similarly encouraging — long-term follow-up data published in the New England Journal of Medicine in October 2025 showed a 95% success rate in the 62 children treated, with no serious complications reported.
"Hopefully, an approval like this one will encourage other companies to invest in these kinds of therapies and recognize that there is a pathway to make these commercially available," Kohn said. "We've reached a point where it's not the science that's limiting more of these therapies from becoming available, but rather commercial investment. This could help turn that tide."
