Two months after birth, Eliana Nachem developed a cough that would not go away. Three weeks later, she also started having loose stools, so she went to see her pediatrician.
Eliana had no allergies or gastrointestinal problems; Instead, tests showed a problem with her immune system. At 4 months old, Eliana was diagnosed with severe combined immunodeficiency, or SCID.
Babies born with an extremely rare disease do not develop the cells needed for the immune system. Every germ becomes a potentially deadly threat, and children with this disease must live in a completely sterile environment to stay healthy. Without treatment, children usually do not live past their second birthday.
“I expected the worst, then I immediately started researching,” said Eliana’s father, Jeff Nachem.
The Nachems also began working to make their home a germ-free fortress, reintroducing their pets, never opening windows and opening doors to the outdoors as sparingly as possible. Eliana was kept inside, and the family had disposable gowns, gloves and masks on hand for the rare occasions when visitors came. (SCID is sometimes called “bubble boy disease.”) Eliana also started a temporary treatment that replaced a missing enzyme in her body called adenosine deaminase (ADA).
Following a 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 lead a normal life.
Jeff, Caroline and Eliana Nachem with Dr. Donald Kohn before Eliana’s gene therapy for ADA-SCID. (Courtesy of Caroline Nachem)
Scientists have identified about 20 gene variants that cause SCID. A form of Eliana’s disease, ADA-SCID, is diagnosed in fewer than 10 children born in the United States each year. (Fewer than 100 babies are diagnosed with any form of SCID in any given year.)
In 2014, when she was just 10 months old, Eliana was one of 62 children who participated in a clinical trial of gene therapy for ADA-SCID. Researchers tracked the results of that phase 2 clinical trial in a study published Wednesday in the New England Journal of Medicine. The update reported that all 62 children who were treated between 2012 and 2019 are alive today. In 59 of them, including Eliana, the gene therapy completely restored immune function without the need for any additional treatment, a success rate of 95%.
“This is one of the most successful gene therapy trials for an extremely rare genetic disease that we have,” said Dr. Talal Mousallem, assistant professor of pediatrics at Duke University School of Medicine, who was not present at the trial.
Stem cell correction
Treatment begins with doctors taking stem cells from the patient’s own bone marrow. These stem cells are purified in the laboratory and then modified using an inactivated form of the virus that causes HIV. Instead of human immunodeficiency virus, this version has the ADA gene, which is missing in people with ADA-SCID, and this gene is inserted back into the DNA of the stem cells.
Before the individual treatment can be re-injected into the patient, they must undergo chemotherapy to get rid of the body’s existing stem cells and make room for new ones. After returning to the body, the cells, which no longer carry the virus, but only the gene it left behind, begin to build the immune system in the coming years.
“It’s a one-time delivery device that puts the gene into the stem cell’s DNA, so every time it divides to make other cells, those cells carry that ADA gene,” said study lead author Donald Kohn, a pediatric bone marrow transplant physician at the UCLA Broad Stem Cell Research Center.
A less risky option
Clinical trials are underway for gene therapy for the four subtypes of SCID, but the standard of care is still bone marrow transplants, which build the immune system using donor stem cells. Treatment can be risky and have side effects.
It is ideal for bone marrow transplants between siblings who have about half the same DNA, but two siblings only have about a 25% chance of matching. In most cases, the donor is not a sibling, which puts the donor’s immune cells at risk of attacking the recipient’s body. This phenomenon is called graft-versus-host disease.
The risk of graft-versus-host means that children who receive functioning stem cells from another person must take immunosuppressants after the transplant to prevent the foreign cells from attacking their immune system.
“It slows down progress because you’re suppressing the immune system and trying to build an immune system at the same time,” Kohn said.
People also have to undergo much higher doses of chemotherapy before a donor bone marrow transplant than before gene therapy.
“There can be effects [later in life] from chemotherapy treatment, including effects on growth, the endocrine system, or fertility,” said Whitney Reid, M.D., an attending physician in the department of allergy and immunology at Children’s Hospital of Philadelphia, who was not involved in the study.
With gene therapy, “you can give those patients much lower doses of chemotherapy and there’s a much lower chance of rejection,” she said.
Eliana “was able to go from living in isolation to going to preschool, swimming in the public pool, playing on the playground and doing everything any other child can do,” her father said. (Courtesy of Caroline Nachem)
Having another treatment for ADA-SCID is especially important, Reid added. Changes in the ADA gene cause toxins to accumulate in clumps of white blood cells called lymphocytes. This can lead to hearing loss and learning difficulties as children get older.
Unlike other types of SCID, “it doesn’t just affect the immune system,” Reid said.
Duke University’s Mousallem said he hopes the success of the trial will open the door to gene therapy for other rare diseases that often go untreated, as well as SCID, which is caused by other gene variants.
“The data is well suited to ADA-SCID, and we hope that one day it will become the standard of care,” he said.
Eliana will be 12 next week and loves taking dance lessons.
“It’s amazing that she was able to go from a life of isolation to go to preschool, swim in the public pool, play on the playground and do everything any other child can do,” her father said.
Eliana still gets tested twice a year to make sure her immune system hasn’t weakened. So far so good.
“We think of it as a lifelong therapy,” Kohn said. “Some of these kids are now 15 and living normal lives. We treated them when they were little babies, and now they’re going to graduation.”
This article was originally published on NBCNews.com