Gene therapy for leukocyte adhesion deficiency type I approved

The U.S. Food and Drug Administration (FDA) approved a gene therapy treatment for leukocyte adhesion deficiency type I (LAD1), a very rare and life-threatening primary immunodeficiency (PI). Developed by Rocket Pharma, marnetegragene autotemcel (trade name Kresladi) is approved for pediatric patients with LAD1 who don’t have a stem cell-matched sibling donor. Variants in the ITGB2 gene that prevent white blood cells from clearing infections cause LAD1. The condition affects about one in one million children globally.

Children with LAD1 develop frequent bacterial and fungal infections that are often fatal unless the underlying PI is treated with hematopoietic stem cell transplantation (HSCT; also known as bone marrow transplant) with stem cells from a matched sibling donor. For those patients without a matched donor, gene therapy is an option.

Kresladi is an ex vivo gene addition gene therapy. This means that doctors remove a patient’s own blood-forming stem cells, add a healthy copy of the ITGB2 gene to the stem cells, and then return the modified cells back to the patient. The modified stem cells multiply and create working white blood cells, providing the individual with a functioning immune system.

University of California Los Angeles (UCLA) researcher Dr. Donald Kohn, who has developed gene therapy for rare immune disorders for more than three decades, led the LAD1 gene therapy clinical trial. Nine patients aged 5 months to 9 years with severe LAD1 enrolled in the trial. Because LAD1 affects about one in one million children globally, cases are rare. Investigators treated six patients at UCLA and three in London and Spain.

Published in April 2025, the clinical trial results showed all patients had continued, stable recovery of their immune systems after the treatment over a period of two years. In fact, immune function approached normal levels.

“The therapy is truly transformative and so beneficial for all of the patients who received it, so that is fantastic,” said Kohn. “And all of the patients we treated at UCLA and their parents were so wonderful. They spent 2-3 months with us over the course of evaluation, stem cell collection, and the transplant. So, we got to know each other well.”

The Langenhops were one of those families. Parents Alicia and Jon Langenhop enrolled their three children, Ava, Olivia, and Landon—all diagnosed with LAD1. Overwhelmed with illnesses, hospitalizations, and medical costs, the Langenhops chose gene therapy because patients with LAD1 who receive HSCT have only a 75% survival rate.

“Gene therapy has truly been life-changing in the best way possible for our children. Before treatment, our lives revolved around illness, doctor visits, and constant fear of infections. Now, they live like typical kids, going to school, playing sports, and just enjoying being children. Their health today is something we once only hoped for, and gene therapy made that possible,” said Alicia Langehop.

“There are no words that could express how unbelievably grateful we are to Dr. Kohn and his team. Because of their dedication, research, and belief in this therapy, our children have a future that once felt uncertain,” said Alicia Langenhop.

Kresladi is the second gene therapy approved by the FDA for a PI in the last five months. In December 2025, the FDA approved Waskyra, a gene therapy to treat Wiskott-Aldrich syndrome (WAS) in both children and adults. An Italy-based non-profit, Fondazione Telethon, developed the treatment.

A gene therapy for another PI— adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID)—has been in clinical trials for over two decades at UCLA. While every gene therapy program is critically evaluated by the FDA and there are no guarantees, said Kohn, Kresaldi’s approval could signal that the FDA is open to covering therapies for patients with rare diseases based on studies in small numbers of patients, if the outcome is strong.

“For the patients with inborn errors of immunity, this approval may increase hope for gene therapies for many other disorders,” said Kohn.

The Langenhops thanked the FDA for recognizing the importance of Kresaldi. Children with LAD1 who cannot find a stem cell donor can now grow up healthy, attend school, and experience a normal childhood, they said. Having the treatment lifts the emotional and physical burden from families who live in constant worry.

“When we heard about the FDA approval, we felt overwhelming gratitude and relief. We felt so fortunate to have been helped by this treatment, and the best-case outcome was for it to become available to help other children too. Knowing that more families will now have access to this treatment is incredibly meaningful. It’s a huge step forward for the entire rare disease community,” said Alicia Langenhop.

“This approval represents more than medical advancement. It represents hope. For families facing a diagnosis like LAD1, it can feel isolating and overwhelming, especially when treatment options are limited or non-existent. Knowing there is now an approved treatment brings comfort and possibility. We’re incredibly grateful that our children were able to be part of this journey, and we’re hopeful for all the families who will benefit from it in the future.”