Two years after receiving an investigational gene therapy, nine children diagnosed with severe leukocyte adhesion deficiency-I (LAD-I) are living without symptoms of the disease. This outcome emerged from an international clinical trial co-led by UCLA’s Dr. Donald Kohn.
LAD-I is a genetic disorder resulting from mutations in the CD18 gene, crucial for white blood cells to reach infection sites. Without treatment, affected individuals suffer recurrent infections and rarely survive beyond childhood. The trial, documented in the New England Journal of Medicine, involved nine children aged from five months to nine years, treated across three clinical sites: UCLA Mattel Children’s Hospital, Great Ormond Street Hospital in London, and the Hospital Infantil Universitario Niño Jesús in Madrid.
Participants responded positively, with resolved skin lesions and gum inflammations, now comparable in health to peers with normal immune systems. “These children are no longer defined by their diagnosis,” said Kohn, emphasizing freed lives from severe infections and reduced hospital visits.
The investigational therapy, designed by Rocket Pharmaceuticals, Inc., substitutes the need for bone marrow transplants, which carry risks like graft-versus-host disease. The therapy involves collecting and amending the patient’s blood stem cells with a lentiviral vector carrying a healthy copy of the CD18 gene. These cells are reintroduced to produce functioning immune cells.
Reports by Kohn and his colleagues show all patients achieved sufficient CD18 protein levels, normalized white blood cell counts, and fewer severe infections requiring hospitalization, with no significant adverse effects observed.
Future steps involve long-term follow-up for six children under UCLA’s oversight, with a 15-year monitoring plan to assess ongoing efficacy and safety. The U.S. Food and Drug Administration is currently reviewing the therapy’s Biologics License Application.
“This therapy presents a new path forward in treating these rare immune conditions and reducing the burdens and risks for patients,” stated Dr. Claire Booth at GOSH. “It’s a momentous breakthrough for families facing this devastating disease.”
Among the trial’s participants, the Langenhop family’s experience was particularly notable. Siblings Ava, Olivia, and Landon Langenhop enrolled in the trial at UCLA during the COVID-19 pandemic. “Every fever, every rash was terrifying,” their mother Alicia shared about their past struggles. However, following participation in the trial, the siblings are now able to engage in daily activities such as attending school and playing outdoors, highlighting a profound transition from consistent medical care to normal childhood experiences.
The investigational lentiviral gene therapy, currently unapproved for clinical use, is developed by Rocket Pharmaceuticals, Inc. The research was funded in partnership with the California Institute for Regenerative Medicine.
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