Imagine a life encased in a "bubble", not allowed to breath in, touch, nor taste much of anything. This could have been the life of seven babies if not for science.
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 a called X-linked severe combined immunodeficiency (SCID-X1), it causes mutations in a gene that is crucial for immune-system development. The disorder leaves the immune system of affected children severely underdeveloped that even a common cold can be fatal. SCID-X1 and other related disorders are also known as 'bubble boy' diseases because of the plastic enclosure that were used to protect affected children from infection.
The treatment involves replacement of the mutated gene with a corrected copy called IL2RG. The results of the research was published on 17 April in The New England Journal of Medicine. It showed that seven babies that were part of the study now have immune system 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 available for these children is bone-marrow transplantation from a matched sibling donor, though that option is only possible to very few (20%).
Researchers have been trying for almost two decades to develop a way of replacing the mutated gene with a functional copy, most particularly for affected children who can't receive such a transplant.
Not all results of the said research were positive. Early trials did partially improve immune responses but some of the patients developed leukemia. Follow-up studies also showed partial improvement of immune responses but they altered a virus that they were using to shuttle functional copies of the corrected gene. The upside though was that none of the patients developed leukemia.
For the latest trial, Mamcarz and her colleagues used yet another virus, this time a disabled relative of HIV, which is more adept than the 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 children have shown no signs of leukaemia up to two years after their treatment. Although a few cases of leukaemia developed after two years in previous studies. The children in the 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 and are long term", 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."
