Gene Therapy Revolutionizes Treatment for Rare Immune Deficiency
in a groundbreaking progress, an international team of researchers has successfully restored immune function in children diagnosed with severe leukocyte adhesion deficiency type I (LAD-I), a rare and life-threatening genetic disorder. The experimental gene therapy offers a promising new therapeutic avenue, potentially redefining treatments for rare genetic diseases affecting the immune system.
Understanding LAD-I: A Rare Genetic Challenge
LAD-I affects approximately one in a million people worldwide. This genetic condition stems from mutations in the gene responsible for producing CD18, a crucial protein that enables white blood cells to migrate from the bloodstream to sites of infection. Without functional CD18, individuals with severe LAD-I are highly susceptible to recurrent bacterial and fungal infections, often diagnosed within the first months of life. Historically, survival beyond childhood has been rare without aggressive treatment.
Did You Know?
The only treatment currently available for LAD-I is a bone marrow transplant from a compatible donor. However,this procedure carries significant risks,including graft-versus-host disease,where the donated cells attack the patient’s body.
The Breakthrough: Gene Therapy Restores Immune Function
The international clinical study,coordinated by the University of California,Los Angeles (UCLA),demonstrated that an experimental gene therapy successfully restored immune function in all nine children treated for this rare form of type I leukocyte deficiency. The findings, published in the New England Journal of Medicine, detail the two-year outcomes for patients aged 5 months to 9 years who received the therapy at UCLA mattel Children’s Hospital, Great Ormond Street Hospital (GOSH) in London, and Hospital Infantil Universitario Niño Jesús in Madrid.
Remarkable Results: A Life-Changing Transformation
All nine children participating in the study exhibited positive responses to the treatment and now live without symptoms of LAD-I.Distinctive signs of the disease, such as skin lesions and severe gingivitis, have completely disappeared.These children can now effectively combat infections, mirroring the immune responses of healthy individuals.
These children are no longer defined by the diagnosis.The fact that thay are healthy and develop without serious infections and without frequent visits to the hospital demonstrates how effective this therapy is.
Dr. Donald Kohn, professor of microbiology, immunology and molecular genetics and researcher at Eli and Edythe broad Center, UCLA
How the Gene Therapy Works
Developed by rocket Pharmaceuticals, this experimental therapy genetically modifies the patient’s own stem cells, effectively turning them into their own stem cell donors and mitigating many of the risks associated with traditional transplants.The process involves:
- Harvesting hematopoietic stem cells from the patient.
- Modifying these cells using a lentiviral vector, a modified virus designed to safely introduce genetic material into cells.
- The vector delivers a functional copy of the CD18-encoding gene to the patient’s stem cells.
- Reinfusing the modified stem cells into the patient’s body, enabling the production of healthy immune cells capable of fighting infections.
Positive Outcomes and Long-Term Monitoring
The UCLA team reported that all patients achieved adequate CD18 protein levels, a normal count of white blood cells, and a significant reduction in severe infections requiring hospitalization. Importantly,no severe adverse reactions to the gene therapy were observed,and all patients continue to maintain a functional graft without adverse immune reactions.
Six of the nine patients have enrolled in a 15-year long-term tracking study at UCLA to assess the sustained effectiveness and safety of the therapy.
The Future of Gene Therapy for Rare Genetic Disorders
The study’s results underscore the potential of gene therapy to provide lasting benefits, with a deep impact on patients’ lives
for individuals with rare genetic disorders, according to Dr. Kohn, who also serves as a pediatric teacher, molecular and medical pharmacology expert at the David Geffen School of Medicine within UCLA.
This experimental gene therapy represents a significant advancement in treating rare immune system conditions, reducing the burden and risks for patients. The treatment is currently under evaluation by the Food and Drug Administration (FDA) in the United States.
