Imagine a life where every breath could be your last. For Eliana Nachem, this was a terrifying reality. Born with a severe immune deficiency, she was once confined to a sterile bubble to survive. But now, thanks to groundbreaking gene therapy, she's thriving, living a normal life. This is her incredible story.
Eliana's journey began with a persistent cough at just two months old. Soon after, gastrointestinal issues emerged, leading her parents to seek medical help. The diagnosis was devastating: severe combined immunodeficiency, or SCID.
Babies with SCID are born without the cells needed for a functional immune system. This means every germ, every common cold, poses a life-threatening risk. Without treatment, most children with SCID don't live past their second birthday.
"I expected the worst, then I immediately went into research mode," Eliana's father, Jeff Nachem, recalls. The Nachems sprang into action, transforming their home into a germ-free sanctuary. They rehomed their pets, sealed the windows, and limited outside exposure. Visitors were required to wear disposable gowns, gloves, and masks. (SCID is sometimes referred to as “bubble boy disease.”) Eliana also started on a temporary therapy that replaced a missing enzyme in her body, called adenosine deaminase (ADA).
Amidst this challenging environment, the family learned about a clinical trial in Los Angeles, 2,600 miles away, offering a glimmer of hope. Scientists have identified approximately 20 gene variants that cause SCID. Eliana's specific form, ADA-SCID, affects fewer than 10 children born in the U.S. each year. (Fewer than 100 babies are diagnosed with any form of SCID annually.)
In 2014, at just 10 months old, Eliana became one of 62 children enrolled in a gene therapy trial for ADA-SCID. The results, published in the New England Journal of Medicine, are nothing short of miraculous. Researchers followed up on the trial, and the results are incredible: all 62 children who received the treatment between 2012 and 2019 are still alive. In 59 of them, including Eliana, the gene therapy completely restored immune function, without any further treatment – a stunning 95% success rate.
"This is one of the most successful gene therapy trials for an ultra-rare genetic disease that we have," says Dr. Talal Mousallem, an associate professor of pediatrics at Duke University School of Medicine. (He was not involved with the trial.)
So, how does this life-saving treatment work? The process starts with doctors harvesting stem cells from the patient's bone marrow. These cells are then purified and modified in a lab using an inactivated form of the HIV virus. This modified virus carries the ADA gene, which is missing in those with ADA-SCID, and reinserts it into the stem cell DNA.
Before the modified cells are reintroduced, patients undergo chemotherapy to eliminate their existing stem cells, making way for the new ones. Once back in the body, the cells – now carrying the ADA gene – begin building a functional immune system over the next year.
"It’s a one-time delivery vehicle that takes the gene into the DNA of the stem cell, so every time it divides to make other cells, those cells carry that ADA gene," explains Dr. Donald Kohn, a pediatric bone marrow transplant physician at UCLA’s Broad Stem Cell Research Center, who led the trial.
But here's where it gets controversial... While gene therapy trials are underway for several SCID subtypes, the current standard of care is still a bone marrow transplant, which uses donor stem cells to build an immune system. However, this approach can be risky.
Ideally, bone marrow transplants are done between siblings, who share about half of the same DNA. But siblings only have about a 25% chance of being a match. When the donor isn't a sibling, the risk increases that the donor's immune cells will attack the recipient's body, a condition known as graft-versus-host disease.
This risk means patients who receive donor stem cells must take immunosuppressant drugs to prevent their bodies from rejecting the new cells. "Which slows down the progress, because you are suppressing the immune system while also trying to build an immune system," Dr. Kohn explains.
Furthermore, patients undergoing bone marrow transplants require higher doses of chemotherapy than those undergoing gene therapy. "There can be effects [later in life] from being treated with chemotherapy, including growth, endocrine or fertility effects," notes Dr. Whitney Reid, an attending physician at Children’s Hospital of Philadelphia.
Gene therapy, on the other hand, allows for lower doses of chemotherapy and reduces the risk of rejection. This is especially important for ADA-SCID, where changes in the ADA gene can cause toxins to accumulate, leading to hearing loss and learning difficulties. Unlike other SCID types, ADA-SCID affects more than just the immune system.
Mousallem hopes the trial's success will pave the way for gene therapies for other rare, often untreated, diseases, including other SCID variants.
Eliana is turning 12 next week and enjoys dance classes. Her father reflects on the incredible transformation: "It’s amazing that 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." Eliana continues to undergo twice-yearly tests to monitor her immune system. So far, so good.
"We think it’s a lifelong therapy," Dr. Kohn states. "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."
What are your thoughts on this revolutionary treatment? Do you think gene therapy is the future of medicine? Share your opinions in the comments below!
