Babies born without an immune system can get a lab-made one

A common cold was enough to kill Cora Oakley. Born in Morristown, New Jersey, with virtually no immune system, Cora was diagnosed with severe combined immunodeficiency (SCID), a rare genetic condition that leaves the body without key white blood cells. It’s better known as “bubble boy disease”, popularised 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 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 US, 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,” 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% of these children, including Cora, it fully restored their immune systems.


Today, gene therapies are being tested for four of SCID’s 20 subtypes, and 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.”


How the therapy works


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 Human Immunodefiency Virus (HIV) as the courier. (The virus can’t replicate but is excellent at integrating its genetic cargo into cells’ DNA.) The corrected stem cells are then returned to the babies, where they can produce healthy immune cells.


With this treatment, babies need only a low dose of chemotherapy, said Dr Donald Kohn, a paediatric immunologist at UCLA Health who led the new study. 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 with what doctors usually see with bone-marrow transplants, he added.

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,” Kohn 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, a 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.


Cost runs up to millions


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, said Dr Susan Prockop, a paediatric hematologist and oncologist at Boston Children’s Hospital.


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,” Prockop added, but that doesn’t mean much if families can’t get it.


For now, Cora’s life is delightfully ordinary, Ferrier said. She has become a fearless 8-year-old who wants to volunteer with kittens who don’t have homes and 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,” Ferrier said, “if Cora didn’t have this opportunity.” NYT News Service