Innovative Gene Therapy Offers New Hope for Children with Rare Immune Disorder

An emerging gene therapy has demonstrated remarkable success in restoring immune system function in children suffering from severe leukocyte adhesion deficiency-I (LAD-I), a rare and life-threatening immune disorder. This groundbreaking clinical trial, led by researchers at UCLA and international partners, involved nine children aged between 5 months and 9 years. All participants experienced complete recovery of immune function, with resolution of skin lesions and gum inflammation, and were able to combat infections effectively.

LAD-I is an ultra-rare genetic condition affecting approximately one in a million individuals worldwide. It results from mutations in the gene encoding CD18, a protein essential for white blood cells to migrate from the bloodstream to infection sites. Without functional CD18, patients are highly susceptible to recurrent bacterial and fungal infections, often experiencing severe health complications early in life, with survival beyond childhood being uncommon without intervention.

The study, published in the New England Journal of Medicine, reports two-year follow-up results showing all treated children had sufficient levels of the CD18 protein, normalized white blood cell counts, and a significant decrease in severe infections requiring hospitalization. Importantly, no serious adverse effects related to the gene therapy were observed. The therapy involves collecting patients’ blood stem cells, genetically correcting them using a lentiviral vector that introduces a healthy copy of the CD18 gene, and reinfusing these cells into the patient. This process enables patients’ bodies to produce healthy immune cells capable of fighting infections.

Compared to traditional treatment options like bone marrow transplants—which carry risks such as graft-versus-host disease—this investigational gene therapy offers a personalized approach that potentially reduces complications. The six patients enrolled in long-term follow-up will be monitored over 15 years to assess the therapy’s durability and safety.

Lead researcher Dr. Donald Kohn from UCLA emphasizes that this innovative approach could change the treatment landscape for rare genetic disorders like LAD-I. The therapy is currently under review by the U.S. Food and Drug Administration, with approval potentially expanding access for more patients in need.

This development marks a significant step forward in gene therapy, offering hope for children with otherwise intractable immune deficiencies and demonstrating the potential for lifelong health benefits through targeted genetic correction.