Researchers at the University of California, Los Angeles conducted a first in kind study on nine children aged five to nine who live with a rare congenital immune disorder known as LAD-I. The study tested an experimental genetic therapy designed to correct the underlying defect in their immune system. The work was reported in a major medical journal, underscoring a significant step forward in how this condition might be treated in the future. The team chose children within this narrow age range because early intervention can shape how the immune system develops while controlling infections that can be life threatening. The approach leaned on the patients’ own biology, aiming to maximize compatibility and minimize complications related to donor immune cells. The results offer a glimpse into what might be possible when a precise genetic fix is paired with a patient’s own immune system in pediatric care.
LAD-I, or Leukocyte Adhesion Deficiency type I, is extraordinarily rare, occurring in roughly one in a million individuals. It arises from mutations in the CD18 gene, a critical part of the molecules that let white blood cells migrate to sites of infection. Without a functioning CD18 protein, leukocytes struggle to reach and attack invading pathogens, leaving children vulnerable to persistent infections. In the absence of effective therapy, many affected children face severe health challenges that can limit growth and, in the worst cases, shorten lifespan. Historically, bone marrow transplantation has been used to restore immune function in LAD-I, but the procedure carries substantial risks. Graft-versus-host disease, rejection of donor cells, and other complications can threaten safety and quality of life. These realities have driven researchers to pursue alternatives that maintain the body’s own cells and harness genetic repair, potentially offering durable benefits with fewer risks.
The therapeutic strategy centers on the child’s own stem cells. Blood is drawn and the stem cell fraction is isolated. A safe viral vector delivers a corrected version of the CD18 gene into those cells, enabling them to develop into immune cells capable of producing the CD18 protein. After the modification, the cells are returned to the patient, where they home to the bone marrow and begin to repopulate the immune system. In this model, the gene correction travels with every new generation of immune cells, creating a lasting pool of healthier leukocytes designed to patrol for infections. The process balances novelty with safety, emphasizing controlled editing and mature quality checks before cells reenter the circulation.
Early observations reported striking clinical improvements. Chronic infections eased as infections were controlled more effectively; skin lesions began to heal, and inflammatory signs diminished. Laboratory tests showed that the CD18 protein levels in leukocytes rose toward normal values, and total white blood cell counts aligned with those seen in healthy peers. Importantly, the therapy did not produce serious side effects in the monitored period, a finding that supports the feasibility of autologous gene transfer in this young population. Families and clinicians noted meaningful gains in daily living and resilience against common infection triggers. The absence of major adverse events during the follow up period provides reassurance about the approach’s short to mid term safety profile.
Long term monitoring was possible for six of the nine participants, with some follow ups spanning up to fifteen years. This extended observation allowed researchers to assess sustained immune function, durability of the genetic correction, and late effects on growth and development. The data suggested that the therapy could maintain immune competence without ongoing interference or need for repeated interventions. While the results are encouraging, researchers emphasize the need for broader trials to confirm safety and efficacy across diverse patient groups and to refine dosing, timing, and monitoring. The study also illustrates how leveraging a patient’s own cells may reduce dependence on donor therapies and might shift how clinicians approach severe immunodeficiencies in children.
The progress aligns with a broader shift in medicine toward gene based treatments that use a patient’s own cells to repair defective pathways. Earlier research faced hurdles in achieving durable immune restoration, but the nine patient experience demonstrates a potential blueprint for applying this technology beyond LAD-I. If confirmed in larger studies, autologous gene therapy could offer a safer, more accessible option for children who previously faced limited choices. The work also raises important ethical and practical questions about early intervention, long term follow up, and equitable access to advanced therapies. In summary, this milestone reveals how precise genetic correction, delivered to a patient’s own cells, can transform the trajectory of a serious congenital immunodeficiency and provide a model for future pediatric applications. Citation: UCLA study.