A four-year-old boy with an ultra-rare immune disorder that typically carries a "death sentence" is now enjoying a normal childhood after participating in a groundbreaking gene therapy trial that has transformed his life.
Eisa Hussain from Reading, UK, was born with a severe form of leukocyte adhesion deficiency 1 (LAD-1), an inherited genetic disorder that critically impairs the immune system's ability to fight infections. Without treatment, children with severe LAD-1 typically die before the age of two.
"From previous studies on patients with this condition, if you have less than 2% expression [of the CD18 protein], it's essentially like a death sentence without any treatment," explained Professor Claire Booth, consultant paediatric immunologist at Great Ormond Street Hospital (GOSH).
The Breakthrough Treatment
The innovative gene therapy works by modifying the patient's own stem cells to help them create the missing protein—CD18—needed for proper immune function. These modified cells are then returned to the patient, helping them develop a functioning immune system.
Eisa received the treatment in January 2021 when he was just 10 months old, after his parents noticed something was wrong shortly after his birth during the early days of the pandemic lockdown.
"Great Ormond Street told us they couldn't find a bone marrow match so they offered the gene therapy. I said 'if that's the only option they have, we have to do it,'" recounted Safdar Hussain, Eisa's father.
Prior to this new therapy, the only treatment option for LAD-1 was a stem cell transplant from a closely matched donor—which wasn't available for Eisa. The gene therapy approach eliminates the risk of rejection or graft-versus-host disease that can occur with donor transplants.
Understanding LAD-1
LAD-1 is caused by a mutation in the ITGB2 gene, which is responsible for producing the CD18 protein found on neutrophils—white blood cells that act as the body's "first line of defense" against infections.
The severity of LAD-1 is determined by how much CD18 a person expresses. Those with less than 2% expression, like Eisa, have the most severe form of the disease. Medical experts note that patients who can achieve levels above 10-15% typically do well.
"We know if you can get above 10% or 15% then those patients actually do well, so we had something to aim for," said Professor Booth, who is also a professor in gene therapy and paediatric immunology at UCL.
Remarkable Results
The clinical trial, sponsored by Rocket Pharmaceuticals, included nine children with severe LAD-1 from centers around the world, with two patients treated at GOSH.
Findings published in the New England Journal of Medicine revealed that all participants survived to the two-year follow-up mark—a significant achievement for a condition that is typically fatal in early childhood without intervention.
After treatment, all children showed the presence of the CD18 protein needed to fight infections long-term, allowing them to stop taking preventative medications. The researchers reported reduced infections, fewer infection-related hospital admissions, and normal wound healing in all participants.
The study found "sustained clinical benefit in all patients," with CD18 expression improving to at least 10% in all cases, with some reaching levels as high as 82% compared to healthy cells.
A New Life for Eisa
The transformation in Eisa's life has been remarkable. Once facing a grim prognosis, he now enjoys playing football around the house, attends school, and is developing like other children his age.
"How he is now is better than I could have ever thought he would be—I never thought he would be able to walk, the next thing for us will be talking," said Mr. Hussain.
The treatment also resolved a critical "catch-22" situation for Eisa, who needed surgery for a heart condition but couldn't undergo the procedure due to LAD-1's impact on wound healing. Following the successful gene therapy, Eisa was able to have his heart procedure without complications.
"I saw Eisa last week and to see him essentially living a normal life—without hospital admissions, without preventative medicines, back to a family life where they can go out and do things with their siblings and their family—that's what feels really good," Professor Booth noted.
Future Implications
The success of this trial opens doors for gene therapy applications in numerous other conditions, including cancer and muscular dystrophy.
"The possibilities are really far-reaching," Professor Booth added.
While the treatment has been largely successful, it's worth noting that Eisa experienced hearing loss—a side effect of the chemotherapy he received before the gene therapy to prepare his bone marrow for the modified cells.
Most participants have enrolled in long-term follow-up studies that will track their progress for up to 15 years, providing valuable data on the durability and long-term safety of this groundbreaking approach.
For the Hussain family, the treatment has transformed their lives and given Eisa opportunities they never thought possible.
"Great Ormond Street saved his life," Mr. Hussain said. "He wouldn't be able to have the life he has now without those services."
