Gene Therapy Shows Promising Results in Children with Rare Immune Disorder LAD-I
核心洞察
An investigational gene therapy has successfully restored immune function in all nine children treated for severe leukocyte adhesion deficiency-I (搜索) (LAD-I (搜索)) in an international clinical trial co-led by UCLA.
The therapy genetically corrects patients' own blood stem cells, potentially eliminating many risks associated with traditional bone marrow transplants while effectively treating this rare disorder that affects one in a million people.
All treated children now live symptom-free with normalized white blood cell counts, significantly fewer severe infections, and resolution of characteristic skin lesions and gum inflammation.
Nine children with a rare and life-threatening immune disorder are now living normal lives thanks to an investigational gene therapy that has successfully restored their immune function. The international clinical trial, co-led by UCLA, treated patients with severe leukocyte adhesion deficiency-I (搜索) (LAD-I (搜索)), a genetic condition affecting approximately one in a million people worldwide.
Results from the two-year follow-up, published in the New England Journal of Medicine, show that all nine children responded positively to the treatment and are now thriving without disease symptoms. The trial was conducted across three clinical sites: UCLA Mattel Children's Hospital, Great Ormond Street Hospital (搜索) in London, and the Hospital Infantil Universitario Niño Jesús (搜索) in Madrid.
Understanding LAD-I and Its Impact
LAD-I (搜索) is caused by mutations in the gene that produces CD18 (搜索), a crucial protein that enables white blood cells to travel from the bloodstream to infection sites. Without this protein, patients—most diagnosed within their first months of life—suffer from dangerous, recurrent bacterial and fungal infections. Survival beyond childhood is rare without treatment.
Before therapy, patients typically experienced severe skin lesions and inflamed gums, hallmarks of the condition. These symptoms have now resolved in all treated children, who can fight off infections like their peers with healthy immune systems.
"These children are no longer defined by their diagnosis," said Dr. Donald Kohn, senior author of the study and distinguished professor at UCLA. "Seeing them healthy and thriving without serious infections, without frequent hospital visits, is a testament to how consistently beneficial this therapy is."
How the Gene Therapy Works
The only currently available treatment for LAD-I (搜索) is a bone marrow transplant from a matched stem cell donor—a procedure that carries significant risks, including graft-versus-host disease, where donated cells attack the recipient's body. Finding a matched donor is also challenging.
The investigational therapy, developed by Rocket Pharmaceuticals, Inc., offers a potentially safer alternative by genetically correcting patients' own blood stem cells. The process involves:
- Collecting blood stem cells from the patient
- Using a lentiviral vector (a modified virus) to deliver a functional copy of the affected gene coding for CD18 into these cells
- Infusing the corrected cells back into the patient, where they produce healthy immune cells capable of fighting infections
The study reports that all patients now have sufficient levels of the CD18 (搜索) protein, normalized white blood cell counts, and significantly fewer severe infections requiring hospitalization. Importantly, no severe adverse events related to the gene therapy were reported, and all patients remain free of graft failure or adverse immune reactions.
Long-term Monitoring and Regulatory Review
Six of the nine patients have enrolled in a long-term follow-up study through UCLA, where they will be monitored for a total of 15 years each to assess the therapy's sustained efficacy and safety.
The gene therapy is currently under review by the U.S. Food and Drug Administration, which is reviewing the Biologics License Application. A successful outcome would support treating more children with this rare condition.
"This therapy presents a new path forward in treating these rare immune conditions and reducing the burdens and risks for patients," said Dr. Claire Booth, a consultant in pediatric immunology and gene therapy at Great Ormond Street Hospital (搜索) and co-lead author of the study. "It's a momentous breakthrough for families facing this devastating disease."
A Family's Journey: Three Siblings Transformed
Among the trial participants are three siblings—Ava (9), Olivia (7), and Landon (5)—all born with severe LAD-I (搜索). Their parents, Jon and Alicia Langenhop, described their early years as an "uphill battle" filled with relentless infections, emergency hospital visits, and medical uncertainty.
"Every fever, every rash, was terrifying. We were constantly bracing for the worst," Alicia recalled.
In 2020, the family relocated from Ohio to Los Angeles during the height of the COVID-19 pandemic so the children could participate in the gene therapy trial at UCLA. The decision proved life-changing.
Today, the siblings lead vibrant, carefree lives that once seemed impossible. They attend school, play outside, and handle everyday childhood bumps and scrapes with immune systems that are functioning normally. The constant doctor visits and prolonged hospital stays are now a thing of the past.
"They've been through so much together, and it's made them stronger," Alicia said of her children.
Future Implications
The success of this trial underscores the potential of gene therapy to provide "durable, life-changing benefits" for individuals with rare genetic disorders, according to Dr. Kohn. While the therapy has not yet been approved for clinical use by any regulatory authority, the results offer hope for a new standard of care for LAD-I (搜索) patients.
The research was funded in collaboration with the California Institute for Regenerative Medicine, with Rocket Pharmaceuticals, Inc. currently holding the license for this investigational lentiviral gene therapy.