Dr. Donald Cohn has been developing gene therapies for rare pediatric immune disorders for more than 30 years. This week, their role in clinical trials has culminated in the first 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.
This 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 vulnerable to frequent, life-threatening bacterial and fungal infections. Without treatment, survival after childhood is rare.
The approval of the therapy, marketed under the name Creslady, was based on the results of a clinical trial conducted by Cohn, a member of the Eli and Edith Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
Seeing these patients annually for their follow-up visits and seeing that they are no longer battling life-threatening infections has been incredibly meaningful.”
The investigators enrolled nine patients aged 5 months to 9 years with severe LAD-I from around the world. The small group 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 a healthy copy of the ITGB2 gene to each child’s blood stem cells, then returning these cells to that child, enabling their body to produce functional immune cells to fight infections and heal wounds more quickly. By using patients’ own cells, the therapy prevents the risk of immune system rejection associated with donor cells, or graft-versus-host disease.
We have found that for the patients we have treated, this therapy is often associated with fewer short- and long-term toxicities than those associated with bone marrow transplantation, which requires much more chemotherapy and immunosuppressive drugs before and after the transplant.
Dr. Donald Cohn, member of the Eli and Edith Broad Center of Regenerative Medicine and Stem Cell Research
All nine trial patients survived without the need for bone marrow transplantation, and no cases of graft failure or immune rejection occurred. Importantly, the data showed a significant reduction in serious infections that required hospitalization.
The children’s pre-treatment high white blood cell counts, or leukocytosis, steadily improved, and the researchers observed the continued presence of the therapeutic gene and an increase in CD18 and CD11a expression, which is important for immune system function.
From decades of research to FDA approval
The news marks a major milestone for Cohn, who has spent more than three decades developing and testing gene therapies for immune diseases. Creslady will be the first of these treatments involving Cohn to receive FDA approval – an important step to ensure that the treatment can reach patients who need it.
Developed by Rocket Pharmaceuticals, this therapy is expected to be available through specialized treatment centers experienced in ex vivo gene therapy procedures. Confirmation of clinical benefit will be based on the evaluation of long-term follow-up data of treated patients in clinical studies and through a post-marketing registry.
The approval is also a significant win for the California Institute for Regenerative Medicine, or CIRM, the California state agency that funds stem cell and gene therapy research. Founded in 2004 to accelerate stem cell therapy, CIRM co-funded clinical trials for gene therapy in collaboration with Rocket and is now celebrating the first FDA approval made possible through its support.
Cohn 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 fatal immune system disorder called ADA-SCID, or adenosine deaminase-deficiency severe combined immunodeficiency. The results are equally encouraging – long-term follow-up data published in NEJM in October 2025 showed a 95% success rate in 62 children treated, with no serious complications reported.
“Hopefully, this type of approval will encourage other companies to invest in these types of treatments and recognize that there is a path to making these commercially available,” Cohn said. “We have reached a point where it is not the science that is keeping these treatments from becoming available, but commercial investment. This could help turn that tide.”
