A gene therapy offered new hope for children suffering from a rare and potentially fatal immune disorder, according to a recent study published in the New England Journal of Medicine. The study evaluated the outcomes after two years of treatment in nine patients aged between 5 months and 9 years, all of whom survived to the two-year follow-up mark and are living with no disease symptoms, indicating a "sustained clinical benefit in all patients."
Leukocyte Adhesion Deficiency Type I (LAD-I) is an extremely rare genetic disease, occurring in one case per million, caused by a mutation in the gene ITGB2. This mutation leads to the production of a defective protein called CD18, preventing leukocytes from traveling to infection sites and effectively fighting infections. Without treatment, survival beyond childhood is rare for individuals with severe LAD-I, and the most severe cases are often fatal before the age of two.
The only available treatment for patients with severe LAD-I was a bone marrow transplant from a compatible stem cell donor. However, finding a suitable donor is challenging, and transplants carry risks, including potentially deadly side effects such as graft-versus-host disease.
The new therapy uses the patients' own modified stem cells, eliminating the risk of rejection or graft-versus-host disease. It is designed to be applied once and last a lifetime, as the modified cells produce healthy white blood cells. "No safety events or deaths occurred among the trial participants, and no serious adverse events related to the gene therapy were reported," according to The Independent.
"These children are no longer defined by their diagnosis. Seeing them healthy and thriving without serious infections, without frequent hospital visits, is a testament to how consistently beneficial this therapy is," said Dr. Donald Kohn, senior author of the study, according to a press release published on EurekAlert.
One of the patients who benefited from this therapy is four-year-old Eisa Hussain from Reading, Berkshire. Eisa was born with severe LAD-I and had no suitable bone marrow match, prompting his parents to enroll him in the gene therapy trial at Great Ormond Street Hospital (GOSH). "Great Ormond Street saved his life. He wouldn't be able to have the life he has now without those services," his father, Safdar Hussain, told The Independent.
After receiving the therapy, Eisa is now living a normal life, attending school, and playing football. "Because of this treatment, he has actually been able to fight infections himself," Hussain added.
The trial, co-led by the University of California, Los Angeles (UCLA), involved nine children aged between 5 months and 9 years, all of whom had severe cases of LAD-I and were treated at three clinical sites: Mattel Children's Hospital UCLA, Great Ormond Street Hospital in London, and Niño Jesús University Children's Hospital in Madrid.
"It's a momentous breakthrough for families facing this devastating disease," said Dr. Claire Booth, leader of the London trial site, according to EurekAlert. The new gene therapy works by modifying the patient's own immune cells to help them create the missing CD18 protein needed to fight infections.
After being reintroduced into the patient's body, the modified cells produce healthy immune cells capable of fighting infections. All patients in the trial had normalized white blood cell counts, with the number of leukocytes reaching levels comparable to those of healthy peers. Researchers found "durable improvement in neutrophil CD18 expression to levels of at least 10 percent," and some patients reached levels as high as 82 percent compared with healthy cells.
As a result of the treatment, all patients have had chronic infections, skin lesions, and inflammations eliminated, with a reported reduction in infections and fewer infection-related hospital admissions. "All patients showed adequate levels of the CD18 protein needed to fight infections in the long term," added Kohn.
The success of the trial underscores the potential of gene therapy to provide "durable, life-changing benefits" to individuals with rare genetic disorders and is considered a new milestone in international medicine. The gene therapy is currently under review by the US Food and Drug Administration (FDA), which is reviewing the Biologics License Application.
"This therapy presents a new path forward in treating these rare immune conditions and reducing the burdens and risks for patients," added Booth.
The article was written with the assistance of a news analysis system.