A five-month-old boy with severe combined immunodeficiency disease receives care at a California hospital in 2017.Credit: Santiago Mejia/Polaris/eyevine

An experimental gene therapy has restored functioning immune systems to seven young children with a severe disorder that would have sentenced them to a life of isolation to avoid potentially deadly infections. They are now with family at home, and an eighth child is slated to be released from hospital at the end of this week.

The children have mutations in a gene that is crucial for immune-system development, causing a disorder called X-linked severe combined immunodeficiency (SCID-X1). The gene-therapy treatment replaces the mutated gene, called IL2RG, with a corrected copy. SCID-X1 and related disorders are sometimes called ‘bubble-boy’ diseases because of the plastic enclosures that were once used to protect affected children from possible infection. For them, even a common cold can be fatal.

But seven of the babies in the study1, which was published on 17 April in The New England Journal of Medicine, now have immune systems that can protect them against common childhood ailments. “They are all toddlers now, exploring life and attending day cares,” says Ewelina Mamcarz, a physician at St. Jude Children’s Research Hospital in Memphis, Tennessee, and a lead author on the study.

The best treatment currently available for SCID-X1, which predominantly affects boys, is a bone-marrow transplant from a matched sibling donor. But that option is possible for less than 20% of children with the disorder. Researchers have been trying for nearly 20 years to develop a way of delivering a functional copy of the mutated gene to affected children who can’t receive such a transplant.

Those efforts met with mixed results2: the earliest trials partially improved immune responses, but caused leukaemia in some patients. In a follow-up effort3 in 2014, the same researchers altered a virus they had been using to shuttle functional copies of the IL2RG gene into cells. It still produced only partial improvement in immunity, but none of the children who were treated developed leukaemia.

An enduring cure?

For the latest trial, Mamcarz and her colleagues used yet another virus, this time a disabled relative of HIV. This virus is more adept than the ones researchers had previously used at inserting genes into cells that are not actively dividing — making it better suited for use in the slowly dividing stem cells responsible for generating immune cells.

The team also treated the children with a low dose of chemotherapy before the treatment. That approach is also used in another gene therapy for a related disease called ADA-SCID. That therapy was approved by the European Medicines Agency in 2016.

The children treated for SCID-X1 have shown no signs of leukaemia up to two years after their treatment. Although some cases of leukaemia showed up after two years in previous studies, Fischer says that researchers have been using this viral system for other gene-therapy trials for a decade without any signs of leukaemia.

And the ﻿children in the SCID-X1 trial are producing the proper components of a healthy immune system, including T cells, B cells and natural-killer cells. “This is a very nice contribution to the field,” says Alain Fischer at the College of France in Paris, who developed some of the first experimental gene therapies used to treat SCID-X1.

The results are promising, but researchers will need to continue monitoring the children to ensure that the immune capabilities they developed after treatment remain stable, says Marina Cavazzana, who is also working on gene therapies for SCID-X1 at Necker Hospital for Sick Children in Paris.

“From a physiological point of view and from a quality-of-life point of view, this is a cure,” says James Downing, president of St. Jude Children’s. “Will it be a durable cure? Only time will tell.”