Gene therapy is fundamentally transforming the lives of children diagnosed with severe combined immunodeficiency (SCID), including the ‘bubble boy’ disease, by restoring their immune systems and allowing them to thrive outside the sterile environments that once defined their existence.
For decades, severe combined immunodeficiency (SCID), often known as “bubble boy” disease, trapped children in a world of medical isolation, where even a common germ could be fatal. Now, groundbreaking advances in gene therapy are offering a lasting cure, allowing children like Eliana Nachem to live full, unrestricted lives.
Understanding SCID: A Life in Isolation
SCID is a rare, life-threatening genetic disorder where children are born with little or no functioning immune system. Historically, this meant living in highly sterile environments, as vividly portrayed in the 1976 TV movie “The Boy in the Plastic Bubble,” based on the true story of David Vetter, who lived in isolation for nearly 13 years.
Without treatment, infants with SCID are highly vulnerable to life-threatening infections from viruses, bacteria, and fungi, often succumbing to the disease within their first two years of life. Families endure immense challenges, like Eliana’s mother, Caroline, recalling, “We had to get rid of our dog and cat, she couldn’t go outside, and I had to stop breastfeeding.”
The ADA-SCID Breakthrough: A Lasting Cure Takes Hold
One prominent form of the disorder, ADA-SCID (adenosine deaminase severe combined immunodeficiency), is caused by a genetic mutation that inhibits the production of an enzyme essential for immune function. For these children, an experimental gene therapy has delivered remarkable results.
Led by senior researcher Dr. Donald Kohn, a professor at UCLA, a gene therapy trial has successfully cured 59 out of 62 children treated between 2012 and 2019, achieving a 95% success rate. Eliana Nachem, diagnosed at 3 months old, received this therapy at 10 months and has since thrived, attending school and playing basketball without fear of infection. Researchers reported these findings in the New England Journal of Medicine, noting the durability and safety of the treatment.
The therapy works by collecting a child’s own blood stem cells, treating them with a modified virus that implants a healthy copy of the ADA gene, and then infusing these corrected cells back into the child. After a period of 6 months to a year, the immune system typically reaches normal, functional levels. “The durability of immune function, the consistency over time and the continued safety profile are all incredibly encouraging,” Kohn stated in a news release from UCLA.
A significant development for accessibility is the ability to use frozen preparations of corrected stem cells, meaning children can have their cells collected locally and the treatment processed elsewhere, removing the need for extensive travel to specialist centers.
A Legacy of Cures: Gene Therapy for SCID-X1
Another form, X-linked severe combined immunodeficiency (SCID-X1), also known as “bubble boy” disease, has seen similar advancements thanks to the dedicated work of researchers like the late Dr. Brian Sorrentino, experimental hematology director at St. Jude. Dr. Sorrentino, a childhood cancer survivor, dedicated over 20 years to finding a cure for this immune disorder.
SCID-X1 is caused by a mutation in the interleukin-2 receptor subunit gamma (IL2RG) gene. The gene therapy developed by Dr. Sorrentino and his colleagues at St. Jude and UCSF Benioff Children’s Hospital San Francisco uses a re-engineered lentivirus to introduce a normal copy of the IL2RG gene into patients’ blood stem cells, incorporating “insulators” to prevent unintended gene activation.
This approach has yielded outstanding results, with all ten infants treated between 2016 and 2018 now producing functional immune cells, including T cells, B cells, and natural killer (NK) cells, without immediate side effects. Dr. Sorrentino’s legacy lives on in these children, who are now toddlers developing normally and getting vaccinations.
Gene Therapy: A Safer Alternative to Traditional Treatments
The traditional standard of care for SCID has been bone marrow transplantation. While effective for some, it carries significant risks, particularly for the over 80% of SCID patients who lack a tissue-matched sibling donor. Donor transplants often require higher doses of chemotherapy and lifelong immunosuppressant drugs to prevent graft-versus-host disease, where the donor’s immune cells attack the recipient’s body.
Gene therapy, by using the patient’s own corrected stem cells, eliminates the risk of graft-versus-host disease and allows for much lower doses of chemotherapy. As Dr. Whitney Reid, an attending physician at Children’s Hospital of Philadelphia, points out, this minimizes potential long-term side effects such as growth, endocrine, or fertility issues associated with intensive chemotherapy.
The Broader Promise and Future of Gene Therapy
Gene therapy represents a promising frontier in medicine, aiming to fix or replace faulty genes responsible for various diseases. The U.S. Food and Drug Administration (FDA) has already approved several gene therapy products for conditions including certain cancers, spinal muscular atrophy, hemophilia, and sickle cell disease. For many, however, access is still primarily through clinical trials, which are crucial for assessing safety and efficacy.
The success in treating SCID subtypes provides a blueprint for tackling other rare genetic disorders. “The data is great for ADA-SCID, and it is our hope that one day this becomes the standard of care,” said Dr. Talal Mousallem of Duke University School of Medicine. Challenges remain, including optimizing gene delivery, ensuring precise cell targeting, minimizing side effects, and addressing the high costs and insurance coverage.
Despite these hurdles, the journey of children like Eliana, who at 11 years old is now starting sixth grade with dreams of becoming an artist, highlights the immense potential. Her father, Jeff Nachem, marvels, “She was able to go from living in isolation to being able to go to preschool and go swimming in a public pool and play on a playground and do all the things that every other kid gets to do.” As Dr. Kohn confidently states, “We think it’s a lifelong therapy. Some of these kids are now 15 years old and are living normal lives. We treated them when they were little babies, and now they’re going to prom.” This sentiment underscores a future where once-fatal genetic conditions are not just managed, but definitively cured.
