A common cold was enough to kill Cora Oakley.
Born in Morristown, N.J., with virtually no immune system, Cora was diagnosed with severe combined immunodeficiency, a rare genetic condition that leaves the body without key white blood cells.
It’s better known as “bubble boy disease,” popularized by the 1976 movie, “The Boy in the Plastic Bubble.” Although nobody lives inside a plastic bubble anymore, most babies with SCID wouldn’t make it past their first birthday without treatment.
“It seems like you have this perfectly healthy child who’s happy and hitting her milestones,” said Chelsea Ferrier, Cora’s mother. “But no — she is sick, she can’t do anything, she can’t go outside.”
The standard treatment for SCID is a bone-marrow transplant, but it works best with a perfectly compatible sibling donor. Cora was Ms. Ferrier’s first child, her “miracle” after three years of trying and several miscarriages, so she had no brother or sister.
But in 2017, there was a new treatment in clinical trials — a gene therapy that could potentially fix Cora’s stem cells, instead of replacing them with a donor’s. Every year in the United States, up to 100 babies are born with SCID, and this disease can be caused by more than 20 genetic defects. But Cora had ADA-SCID, one of the few types being targeted with gene therapy to restore patients’ immune system.
“I would have sold my organs to get into that trial,” Ms. Ferrier said. Cora got the last spot.
For decades, survival for babies with SCID depended on how quickly doctors could diagnose them and whether they could get a bone-marrow transplant — a lifesaving procedure with often punishing side effects.
But in a study published last month, researchers followed 62 babies with ADA-SCID who received gene therapy and found that, after almost eight years on average, every single one was still alive. In about 95 percent of these children, including Cora, this therapy completely restored their immune systems.
Today, gene therapies are being tested for four of SCID’s 20 subtypes, and should early successes hold, they could collectively treat two-thirds of all babies with the disease.
“This was a fairy tale 20 years ago,” said Frank Staal, a stem cell researcher at Leiden University Medical Center in the Netherlands, who was not involved with this study. “Now it’s a reality.”
From Transplants to Gene Therapy
Bone-marrow transplants have long offered SCID babies a lifeline, keeping them alive but at the risk of serious, sometimes life-threatening side effects.
All newborns in the United States are screened for SCID. And, within a few months of a diagnosis, babies with the disease receive a heavy dose of chemotherapy and then a transplant. This treatment destroys their diseased marrow and opens up spaces for the donor’s stem cells to take root, said Dr. Morton Cowan, a pediatric immunologist at University of California, San Francisco.
Over the next six to 12 months, the new bone marrow starts producing white blood cells, essentially rebuilding the immune system. Recovery, however, can be tenuous: the new cells may not recognize their surroundings and reject the body they’re in, Dr. Staal said — something known as graft-vs-host disease. Many babies receive immunosuppressant drugs to head off this mutiny, but this keeps them vulnerable to deadly infections.
“It’s a paradox — we’re suppressing their immunity when we want their immune system to grow,” said Dr. Donald Kohn, a pediatric immunologist at UCLA Health who led the new study.
Other side effects can unfold over time. Chemotherapy, for instance, can lead to stunted growth, reproductive issues and long-term organ damage.
In search of a safer option, researchers have turned to gene therapy, said Dr. Susan Prockop, a pediatric hematologist and oncologist at Boston Children’s Hospital. Since SCID is caused by a faulty gene, scientists collect babies’ stem cells and, in the lab, introduce a healthy copy, using a harmless, disabled form of H.I.V. as the courier. (While the virus can’t replicate, it is still excellent at integrating its genetic cargo into cells’ D.N.A.) The corrected stem cells are then returned to the babies, where they can grow and produce healthy immune cells.
With this treatment, babies need only a low dose of chemotherapy, Dr. Kohn said, and since doctors are reintroducing their repaired cells, there’s little-to-no risk of rejection or need for immunosuppression. In the new study, the babies recovered more quickly with fewer long-term side effects compared to what doctors usually see with bone-marrow transplants, he added.
Hailey Barlow, who lives in North Salt Lake, Utah, has seen this shift in treatment unfold in her own family. Both of her daughters were born with SCID: Her first, Jaylee got a bone-marrow transplant in 2010 and her second, Hazel, received gene therapy in 2023.
Jaylee spent 11 months in the hospital, getting treatment and then fighting graft-vs-host disease while her parents slept on an air mattress by her side. But Hazel sailed through gene therapy with barely a setback, Ms. Barlow said, home from the hospital just over a month later.
“You really couldn’t even tell Hazel had been sick or had gotten this really important treatment,” she added, while Jaylee had been fighting to stay alive. “The difference between the two treatments was honestly mind boggling,” Ms. Barlow said.
Living With SCID
Even with the new treatment, SCID is a lonely disease: Families must keep their babies away from germs while their immune system is being rebuilt.
“Parents of SCID patients are permanently anxious because they know one infection can take their child from them,” Dr. Kohn said.
For Nicole Haggard, of Ventura, Calif., that anxiety is almost inherited. Over generations, SCID killed most of the boys in her family by the time they were three months old.
Gene therapy gave her son, Dezar, a chance at a normal childhood, but Ms. Haggard’s fear still lingered. Visitors had to change their clothes at the door, the park was off limits and “every decision felt stressful,” Ms. Haggard said.
As Dezar’s immune system recovered and his mother’s confidence grew, their world slowly expanded. But even now, a fever can make Ms. Haggard nervous. “Normal people would just say, ‘My kid’s sick.’ We’re always anticipating it to be something bigger,” she said.
Overall, doctors are optimistic about gene therapy but caution that it’s still new. Bone-marrow transplants have decades of evidence; gene therapy only has years, said Dr. Richard O’Reilly, former chair of pediatrics at Memorial Sloan Kettering Cancer Center. No one can say if the repaired immune systems will hold up over a lifetime, and questions remain about potential long-term risks.
It’s also unclear how many SCID babies will have access to gene therapy, since this treatment can cost millions of dollars per patient, and there’s no pharmaceutical company ready to bring it to market, Dr. Prockop said. For now, this therapy exists only within clinical trials, sustained by a patchwork of nonprofits and state agencies like the California Institute for Regenerative Medicine. But these trials won’t last forever.
“It’s pretty rare that we have disorders that we can completely cure, where the infant never has symptoms,” Dr. Prockop added, but that doesn’t mean much if families can’t get it.
For now, Cora’s life is delightfully ordinary, Ms. Ferrier said. She’s now a fearless 8-year-old who wants to volunteer with kittens who don’t have homes, who begs her mother to pull over whenever she spots a dog, just to know its name.
“I don’t ever want to think about what it would’ve meant,” Ms. Ferrier said, “if Cora didn’t have this opportunity.”
Simar Bajaj covers health and wellness.
The post She Was Born Without an Immune System. Gene Therapy Saved Her Life. appeared first on New York Times.
