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Scientists have used gene therapy to “cure” babies born with a rare, life-threatening immune condition dubbed “bubble boy” disease, otherwise known as X-linked severe combined immunodeficiency (SCID-X1).
The condition was brought to the public spotlight with David Vetter, the boy born in 1971 who spent his life in a plastic bubble to protect his immune system from infection. He died at the age of 12 from a form of cancer called lymphoma, introduced to his delicate immune system by the Epstein-Barr virus. This, it should be noted, is not the standard course of treatment nowadays for those with the disease and has only been used in a few cases.
The patients in the current trial “are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and live normal lives,” said study author Ewelina Mamcarz of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy in the US. “This is a first for patients with SCID-X1.”
The disorder is an inherited condition that almost always occurs in males. Without proper treatment and care, patients have little chance of living past infancy. The disease affects around 1 in 50,000 to 100,000 newborns, according to the NIH. The condition is caused by a mutation in the IL2RG gene, which is responsible for the body’s instruction manual for producing a protein essential for a healthy immune system.
Currently, there is a viable treatment for SCID-X1: a bone marrow transplant. However, this means patients must have a matched sibling donor and less than 20 percent of patients usually do, according to the study authors. Instead, they tend to rely on blood stem cells from donors who are not family, a situation that is better than no treatment but often leads to marked side effects.
The experimental therapy by St. Jude Children's Research Hospital was trailed on eight infants who lacked a matched sibling donor. The team used a modified version of HIV that can’t cause AIDS to deliver the correct gene into the DNA of their blood stem cells, replacing those that do not function correctly.
Two days prior to this, the patients received low-dose busulfan, an agent used in chemotherapy to help make space for donor stem cells to grow in the marrow. The majority of the patients were able to leave the hospital within a month.
The outcome? All the patients are developing normally so far, according to the study, and none have incurred a life-threatening infection. None have developed leukemia either, which was an outcome of previous gene therapy attempts for SCID-X1.
"While longer follow-up is needed to assess any late effects of treatment, these results suggest most patients treated with this gene therapy will develop a complete durable immune response without side effects," said co-author Mort Cowan, a UCSF professor of pediatrics.
Currently, it appears to be a cure. The possibility of these children leading lives unchained by this debilitating condition cannot be overstated. However, only time will tell whether this therapy is truly effective in the long term.
“David’s life showed courage, patience and understanding,” said his mother Carol Ann Demaret at the time to the Immune Deficiency Foundation. “He accepted the unique circumstances of his life, but waited to find the way to come out of his bubble."
David may not have found a way out of his bubble, but thanks to novel gene therapy by scientists at UCSF and St. Jude’s, these children have.
Co-author Stephen Gottschalk added: "We hope this therapy, which includes several novel features, will serve as a template for developing gene therapy to treat other devastating blood disorders.”
