Eliana’s Journey: Living with Severe Combined Immunodeficiency

Two months after her birth, Eliana Nachem developed a persistent cough. Shortly after, she experienced runny stools, prompting a visit to her pediatrician.

Initially, there were no signs of allergies or digestive issues, but tests revealed a significant concern: a problem with her immune system. When she was just 4 months old, Eliana was diagnosed with severe combined immunodeficiency, or SCID.

This extremely rare condition means that babies like Eliana lack the necessary cells for a functional immune system. Essentially, every germ poses a serious risk, and to thrive, these children must remain in a completely sterile environment. Unfortunately, without treatment, many don’t live past age two.

Jeff Nachem, Eliana’s father, expressed his initial feelings: “I expected the worst, then I immediately went into research mode.”

Determined to protect their daughter, the Nachems transformed their home into a fortress against germs. They rehomed pets, avoided opening windows, and limited door use. Eliana remained inside, and when visitors did come over, they had to wear disposable gowns, gloves, and masks. (This condition is sometimes called “bubble boy disease.”) Meanwhile, Eliana began a temporary therapy that provided her with an essential enzyme called adenosine deaminase (ADA).

In the midst of strict precautions, the family discovered a clinical trial in Los Angeles—2,600 miles away from their home in Fredericksburg, Virginia—that could aid in Eliana’s journey toward a normal life.

SCID encompasses around 20 known gene variants. Eliana has ADA-SCID, diagnosed in fewer than 10 U.S. children each year, with overall SCID diagnoses hovering under 100 annually.

In 2014, at just 10 months old, Eliana became one of 62 participants in a clinical trial for gene therapy. A recent study published in the New England Journal of Medicine reported that all 62 children from the trial, who received treatment between 2012 and 2019, are alive today. Notably, 59 of them, including Eliana, had their immune function fully restored without the need for additional treatments—a notable success rate of 95%.

Dr. Talal Mousallem, an associate professor of pediatrics at Duke University School of Medicine, remarked, “This is one of the most successful gene therapy trials for an ultra-rare genetic disease that we have.” He wasn’t directly involved in the trial.

Correcting Stem Cells

The treatment begins with harvesting stem cells from the patient’s own bone marrow. After purifying the cells in a lab, they are modified using a safe version of the HIV virus. Instead of carrying the virus, this form delivers the ADA gene missing in ADA-SCID, integrating it into the stem cell’s DNA.

Before the specialized treatment is reintegrated into the patient, chemotherapy is necessary to eliminate the existing stem cells and create space for the new cells. Once reintroduced, the modified cells, which no longer carry the virus, begin to build an immune system over the subsequent year.

Dr. Donald Kohn, a pediatric bone marrow transplant physician at UCLA’s Broad Stem Cell Research Center and the trial’s leader, explained, “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.”

A Less Risky Option

Gene therapy trials are underway for four SCID subtypes, yet a bone marrow transplant remains the standard care. However, this method can pose significant risks and potential long-term side effects.

Bone marrow transplants are more effective when the donor is a sibling—who shares about half of their DNA—but there’s only a 25% chance of that match between any two siblings. Most donors are not siblings, which raises the risk of the donor’s immune cells attacking the recipient’s body, known as graft-versus-host disease.

Due to this risk, children receiving functioning stem cells from a donor typically need immunosuppressant drugs post-transplant to prevent their immune system from being attacked.

“This slows down the restoration process, because you are suppressing the immune system while also trying to build an immune system,” Kohn noted.

Furthermore, individuals undergoing donor bone marrow transplants must endure much higher chemotherapy doses compared to gene therapy recipients. Dr. Whitney Reid, an attending physician at the Children’s Hospital of Philadelphia, pointed out potential long-term effects from being treated with chemotherapy, like growth, endocrine or fertility issues.

In contrast, gene therapy allows for lower doses of chemotherapy and significantly reduces the chances of rejection, Reid added.

As for Eliana, having alternative therapies for ADA-SCID is crucial. Changes in the ADA gene can lead to harmful toxins accumulating in white blood cells, which might lead to hearing loss and learning challenges as children grow older.

“Unlike other types of SCID, it doesn’t only impact the immune system,” Reid said.

Mousallem expressed hope that the success of this trial paves the way for gene therapies for other rare diseases, as well as SCID caused by various gene variants.

“The data is promising for ADA-SCID, and we hope this becomes the standard of care in the future,” he mentioned.

Eliana, who turns 12 next week, enjoys dancing. Her father said, “It’s incredible that she went from living in isolation to being able to go to preschool, swim in a public pool, play on a playground, and do everything every other kid gets to do.”

She still undergoes testing twice a year to ensure her immune system remains strong. So far, things look promising.

“We think it’s a lifelong therapy,” Kohn explained. “Some of these kids are now 15 years old and are living regular lives. We treated them when they were babies, and now they’re going to prom.”