Gene therapy restores the immune system in 9 children with a rare disease

Nine children between the ages of 5 months and 9 years old with a rare disease have recovered their immune function and seen their lives extended thanks to a gene therapy developed by a team at the University of California, Los Angeles (USA).

The therapy edits and corrects the patient's own stem cells to generate healthy immune cells and avoid the risks of bone marrow transplants.

All nine children are diagnosed with a rare and life-threatening immune disorder called severe leukocyte adhesion deficiency I, or LAD-I.

LAD-I is a genetic disease that affects approximately one in every million people worldwide. It is caused by mutations in the gene that produces CD18, a protein that allows white blood cells to travel from the bloodstream to sites of infection. In the absence of this crucial protein, people with severe LAD-I, most of whom are diagnosed during the first months of life, are vulnerable to recurrent and dangerous bacterial and fungal infections . Survival beyond infancy is rare without treatment.

The study, published in The New England Journal of Medicine , presents two-year outcomes for nine patients aged 5 months to 9 years who received the therapy at three centers: Mattel Children's Hospital at UCLA , Great Ormond Street Hospital in London (GOSH), and the Niño Jesús University Children's Hospital in Madrid .

The nine children in the trial, a small number due to the rarity of the disease, responded well to treatment and are currently living symptom-free.

Their severely inflamed skin lesions and gums, characteristic of LAD-I, have resolved, and they can now fight infections like any child born with healthy immune systems.

The only treatment currently available for LAD-I is a bone marrow transplant from a matched stem cell donor.

For those lucky enough to find a match, bone marrow transplants carry the risk of life-threatening side effects , such as graft-versus-host disease, a condition in which donated cells attack the recipient's body.

The investigational therapy, developed by Rocket Pharmaceuticals, Inc. , genetically corrects patients' blood stem cells, allowing them to become their own stem cell donors and potentially eliminating many of the known risks of bone marrow transplants.

First, the researchers explain in their work, blood stem cells are collected from patients and then modified using a lentiviral vector, a modified virus designed to safely introduce genetic material into cells.

The vector delivers a functional copy of the affected gene encoding CD18 to the patient's blood stem cells, which are then infused back into the patient to produce healthy immune cells capable of fighting infections.

All patients had adequate levels of the CD18 protein, normalized white blood cell counts, and a significant reduction in serious infections requiring hospitalization.

Furthermore, no serious adverse events related to gene therapy were reported, and all patients remained free of graft failure or adverse immune reactions.

The nine patients will be monitored for a total of 15 years to assess the therapy's sustained efficacy and safety.

The trial results underscore the potential for gene therapy to provide “ lasting, life-changing benefits ” to people with rare genetic disorders, said Donald Kohn, the study’s coordinator at UCLA.

The license for this investigational lentiviral gene therapy is currently held by Rocket Pharmaceuticals, Inc. The therapy has not yet been approved for clinical use by any regulatory authority.