Imagine a world where even the slightest exposure to germs could be fatal. That was Eliana's reality for the first few months of her life. But eleven years later, she's thriving, living a life most of us take for granted, all thanks to a groundbreaking gene therapy treatment. How did she go from living in a near-sterile bubble to attending dance classes and birthday parties? Let's delve into her incredible story.
Just two months after Eliana Nachem entered the world, a persistent cough took hold. Three weeks later, coupled with recurring digestive issues, it prompted a visit to her pediatrician. What initially seemed like allergies or a simple stomach bug turned out to be something far more serious.
At just four months old, Eliana received a life-altering diagnosis: severe combined immunodeficiency, or SCID. You might have heard it called "bubble boy disease." In essence, Eliana's body wasn't producing the crucial cells needed for a functioning immune system. And this is the part most people miss: It's not just about catching more colds; for these children, every single microbe, every common cold germ, every seemingly harmless bacteria, becomes a potentially deadly threat. To survive, they must live in a completely sterile environment. Tragically, without treatment, most children with SCID don't live to see their second birthday.
"I expected the worst, then I immediately went into research mode," recalled Eliana's father, Jeff Nachem. Understandably, panic set in quickly, but determination to find a solution replaced the initial fear.
The Nachem family transformed their home into a fortress against germs. They rehomed their beloved pets, sealed the windows shut, and restricted access to the outside world. Eliana remained indoors, and those rare visitors were required to wear disposable gowns, gloves, and masks. Simultaneously, Eliana began a temporary enzyme replacement therapy to compensate for her missing adenosine deaminase (ADA), a crucial element for immune function.
Amidst this strict, isolating protocol, a glimmer of hope emerged: a clinical trial in Los Angeles, a staggering 2,600 miles away from their home in Fredericksburg, Virginia. This trial offered the potential for Eliana to live a normal life. But here's where it gets controversial... While bone marrow transplants are a standard treatment for SCID, they come with their own set of risks and long-term complications. Gene therapy, on the other hand, offered a potentially less risky alternative.
Scientists have identified roughly 20 different gene variants that can cause SCID. Eliana's specific form, ADA-SCID, is particularly rare, affecting fewer than 10 children born in the United States each year. To put it in perspective, less than 100 babies are diagnosed with any form of SCID annually in the US.
In 2014, at the tender age of 10 months, Eliana became one of 62 children to participate in a clinical trial for gene therapy targeting ADA-SCID. A study published in the prestigious New England Journal of Medicine tracked the progress of these children who received the treatment between 2012 and 2019. The results were nothing short of remarkable: all 62 children were alive and well. Even more astonishingly, in 59 of them, including Eliana, the gene therapy had completely restored immune function, eliminating the need for any further treatment. That's a staggering 95% success rate!
"This is one of the most successful gene therapy trials for an ultra-rare genetic disease that we have," declared Dr. Talal Mousallem, an associate professor of pediatrics at the Duke University School of Medicine, emphasizing the significance of this achievement.
So, how does this groundbreaking gene therapy actually work? It's a fascinating process of precision medicine. First, doctors harvest stem cells from the patient's own bone marrow. These stem cells are then purified in a laboratory and carefully modified using an inactivated form of the virus that causes HIV. Don't worry, this isn't as scary as it sounds! The virus is essentially repurposed to act as a delivery vehicle. Instead of carrying the human immunodeficiency virus, this modified version carries the ADA gene that individuals with ADA-SCID are missing. The virus then inserts this healthy gene directly into the stem cell's DNA.
Before the modified stem cells are reintroduced into the patient, a round of chemotherapy is necessary to eliminate the body's existing, faulty stem cells, creating space for the new, gene-corrected cells to thrive. Once back in the body, these modified cells, now carrying the functional ADA gene, begin the crucial work of building a fully functional immune system over the course of the following 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," explained Dr. Donald Kohn, a pediatric bone marrow transplant physician at UCLA's Broad Stem Cell Research Center, who spearheaded the trial. Think of it as a permanent fix, addressing the root cause of the disease.
While gene therapy trials are underway for other types of SCID, the standard treatment remains a bone marrow transplant, which uses stem cells from a donor to build a new immune system. However, bone marrow transplants carry significant risks and potential long-term side effects.
Ideally, bone marrow transplants occur between siblings, who share approximately half of the same DNA, increasing the chances of a successful match. However, siblings only have a 25% chance of being a match. In most cases, the donor is not a sibling, significantly increasing the risk of a potentially life-threatening complication called graft-versus-host disease, where the donor's immune cells attack the recipient's body.
The risk of graft-versus-host disease necessitates the use of immunosuppressant drugs following a bone marrow transplant, which suppress the immune system to prevent the foreign cells from attacking. "Which slows down the progress, because you are suppressing the immune system while also trying to build an immune system," Kohn explained, highlighting the inherent challenges of this approach.
Furthermore, patients undergoing bone marrow transplants typically require much higher doses of chemotherapy compared to those undergoing gene therapy. "There can be effects [later in life] from being treated with chemotherapy, including growth, endocrine or fertility effects," cautioned Dr. Whitney Reid, an attending physician in the division of allergy and immunology at Children's Hospital of Philadelphia.
With gene therapy, "you can give those patients much lower doses of chemotherapy and there is a much lower chance of rejection," Dr. Reid noted, emphasizing the potential advantages of this innovative treatment approach.
Having another viable therapy for ADA-SCID is particularly crucial, Dr. Reid added. Mutations in the ADA gene lead to the accumulation of toxins within white blood cells called lymphocytes, potentially causing hearing loss and learning difficulties as children age. Unlike other forms of SCID, ADA-SCID "doesn't only affect the immune system," highlighting the broader impact of this specific genetic defect.
Dr. Mousallem expressed hope that the success of this trial will pave the way for the development of gene therapies for other rare, often neglected diseases, as well as for other forms of SCID caused by different gene variants. "The data is great for ADA-SCID, and it is our hope that one day this becomes the standard of care," he stated optimistically.
Eliana will celebrate her 12th birthday next week and enjoys attending dance classes. A far cry from the isolated existence she faced as an infant.
"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," her father proudly shared, highlighting the profound impact of this life-saving treatment.
Eliana still undergoes regular testing twice a year to monitor her immune system, but so far, everything looks promising. "We think it's a lifelong therapy," Dr. Kohn stated. "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."
Eliana's story is a testament to the power of scientific innovation and the unwavering dedication of researchers, doctors, and families facing seemingly insurmountable challenges. It also raises important questions about access to these cutting-edge therapies. Should gene therapy be the first line of treatment for ADA-SCID, even if it's more expensive initially? What are the ethical considerations surrounding the use of modified viruses in gene therapy? What do you think? Share your thoughts and opinions in the comments below.
