Two months after she was born, Eliana Nachem got a cough that wouldn’t go away. Three weeks later, she also started having runny stool, prompting a visit to her pediatrician.
Eliana didn’t have allergies or a gastrointestinal condition; instead, tests pointed to a problem with her immune system. At 4 months old, Eliana received her diagnosis: severe combined immunodeficiency, or SCID.
Babies born with the extremely rare disease do not develop the cells required for a functioning immune system. Every germ becomes a potentially fatal threat and to stay healthy, children with the condition must live in a completely sterile environment. Without treatment, kids usually do not live past their second birthday.
“I expected the worst, then I immediately went into research mode,” Eliana’s father, Jeff Nachem, said.
The Nachems also got to work turning their home into a germ-free fortress, rehoming their pets, never opening the windows and opening the doors to outside as sparingly as possible. Eliana was kept inside, and on the rare instance when visitors came by, the family had disposable gowns, gloves and masks for them to wear. (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).
In the midst of the strict protocol, they learned about a clinical trial in Los Angeles — 2,600 miles from their home in Fredericksburg, Virginia — that could help their daughter live a normal life.
Scientists have identified about 20 gene variants that cause SCID. Eliana’s form of the disease, ADA-SCID, is diagnosed in fewer than 10 children born in the U.S. each year. (Under 100 babies are diagnosed with any form of SCID in a given year.)
In 2014, when she was just 10 months old, Eliana was one of 62 children enrolled in a clinical trial for a gene therapy for ADA-SCID. In a study published Wednesday in the New England Journal of Medicine, researchers followed up on the results of that Phase 2 clinical trial. The update reported that all 62 kids, who received the treatment from 2012 to 2019, are alive today. In 59 of them, including Eliana, the gene therapy completely restored immune function, without requiring any additional treatment — a success rate of 95%.
“This is one of the most successful gene therapy trials for an ultra-rare genetic disease that we have,” said Dr. Talal Mousallem, an associate professor of pediatrics at the Duke University School of Medicine. He was not involved with the trial.
Correcting stem cells
The treatment begins with doctors harvesting stem cells from the patient’s own bone marrow. These stem cells are purified in a lab, and then modified using an inactivated form of the virus that causes HIV. Instead of carrying the human immunodeficiency virus, this version carries the ADA gene that people with ADA-SCID are missing, reinserting the gene into the stem cell DNA.
Before the customized treatment is reinfused back into the patient, they must undergo chemotherapy to get rid of the body’s existing stem cells and make room for the new ones. Once back in the body, the cells — which no longer carry the virus, just the gene it left behind — get to work building an 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,” said Dr. Donald Kohn, a pediatric bone marrow transplant physician at UCLA’s Broad Stem Cell Research Center, who led the trial.
A less risky option
Gene therapy clinical trials are underway for four subtypes of SCID, but the standard of care is still a bone marrow transplant, which builds an immune system using stem cells from a donor. The treatment can be risky and side effects further down the line.
It’s ideal for bone marrow transplants to occur between siblings — who share about half of the same DNA — but two siblings only have about a 25% chance of being a match. In most cases, the donor is not a sibling, which introduces the risk that the donor’s immune cells will attack the recipient’s body, a phenomenon called graft-versus-host disease.
The risk of graft-versus-host means kids who receive functioning stem cells from another person have to be on immunosuppressant drugs following the transplant, which keep the foreign cells from attacking their immune system.
“Which slows down the progress, because you are suppressing the immune system while also trying to build an immune system,” Kohn said.
People also have to undergo much higher doses of chemotherapy before receiving a donor bone marrow transplant than they do before undergoing gene therapy.
“There can be effects [later in life] from being treated with chemotherapy, including growth, endocrine or fertility effects,” said Dr. Whitney Reid, an attending physician in the division of allergy and immunology at Children’s Hospital of Philadelphia, who was not involved in the trial.
With gene therapy, “you can give those patients much lower doses of chemotherapy and there is a much lower chance of rejection,” she said.
Having another therapy for ADA-SCID is particularly important, Reid added. Changes in the ADA gene cause toxins to build up in clumps of white blood cells called lymphocytes. This can cause hearing loss and learning difficulties as kids get older.
Unlike other types of SCID, “it doesn’t only affect the immune system,” Reid said.
Mousallem, of Duke University, said he hopes the success of this trial will open the door to gene therapies for other rare diseases that often go untreated, as well as SCID caused by other gene variants.
“The data is great for ADA-SCID, and it is our hope that one day this becomes the standard of care,” he said.
Eliana turns 12 years old next week and loves going to dance classes.
“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 said.
Eliana still undergoes testing twice a year to make sure her immune system hasn’t weakened. So far, so good.
“We think it’s a lifelong therapy,” Kohn said. “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.”
The post Exposure to any germs could’ve killed her. 11 years later, she’s living a normal life thanks to a gene therapy treatment. appeared first on NBC News.
