New Gene Therapy Offers Hope for Children with Rare Immune Disorder

An innovative gene therapy has effectively restored immune function in all nine pediatric patients suffering from severe leukocyte adhesion deficiency-I (LAD-I), a rare and life-threatening immune disorder, according to findings from a multinational clinical trial led by researchers at the University of California, Los Angeles (UCLA).

LAD-I is a genetic disorder that occurs in roughly one in every million individuals globally. It arises from mutations in the gene responsible for producing CD18, a crucial protein that facilitates the movement of white blood cells from the bloodstream to areas of infection. The absence of this protein leaves patients, typically diagnosed within their first months of life, susceptible to severe and recurrent bacterial and fungal infections. Without treatment, survival beyond childhood is uncommon.

In a study published in the New England Journal of Medicine, researchers, including senior author Dr. Donald Kohn, detail the two-year outcomes for nine children aged between 5 months and 9 years who participated in the trial across three sites: UCLA Mattel Children's Hospital, Great Ormond Street Hospital in London, and the Hospital Infantil Universitario Niño Jesús in Madrid. The co-lead authors of the study are Dr. Claire Booth and Dr. Julian Sevilla.

All nine participants in this small-scale trial showed positive responses to the treatment, with no visible symptoms of the disease. The hallmark symptoms of LAD-I, such as skin lesions and severe gum inflammation, have resolved, and these children can now combat infections much like their peers who have healthy immune systems.

According to Kohn, the progress observed in these children signifies a transformative achievement. "These children are no longer defined by their diagnosis," he stated. The ability to see them thriving without serious infections or frequent hospitalizations highlights the consistent efficacy of this therapy.

The only standard treatment currently available for LAD-I is a bone marrow transplant from a compatible donor. However, this option is limited to those fortunate enough to find a matched donor, and it carries significant risks, including life-threatening side effects such as graft-versus-host disease.

The investigational therapy, developed by Rocket Pharmaceuticals, Inc., involves a process where the patient's blood stem cells are collected and genetically modified using a lentiviral vector. This vector is a modified virus designed to safely transport genetic material into cells, delivering a functional copy of the CD18 gene to the patient's blood stem cells, which are then reinfused. This allows the patients to produce healthy immune cells capable of effectively fighting infections.

The study results indicate that all patients achieved adequate levels of the CD18 protein, normalized white blood cell counts, and experienced significantly fewer severe infections that necessitated hospitalization. Importantly, no severe adverse events related to the gene therapy were reported, and all patients remain free from graft failure or adverse immune reactions.

Of the nine children enrolled, six have continued to participate in a long-term follow-up study at UCLA, where they will be monitored over the next 15 years to evaluate the long-term safety and effectiveness of the therapy.

These promising results emphasize the capacity of gene therapy to deliver lasting, life-altering benefits to individuals afflicted with rare genetic disorders. As reported by Kohn, the therapy is currently under evaluation by the U.S. Food and Drug Administration, which is reviewing the Biologics License Application. A favorable outcome could pave the way for treating additional children, enabling them to achieve healthier lives.

Dr. Booth described the therapy as a significant advancement for families grappling with this debilitating condition, stating that it represents a new approach to addressing rare immune disorders and mitigating associated risks for patients.