Fourteen of 16 children with the rare immune disorder sometimes called “bubble boy disease” were well enough to attend school from two to nine years after they were treated, showing the benefit is maintained over time.
The rare illness, affecting about 40 to 100 babies each year, leaves them unable to fight germs, making any infection potentially deadly. Researchers corrected genetic flaws in the children’s bone marrow to enable their immune systems to function, and have followed the children’s progress since.
The therapy may replace bone marrow transplant in treating the disorder since that requires finding a donor and carries risks of graft rejection and graft-versus-host disease, the researchers said. The children’s response over time was reported today in the journal Science Translational Medicine.
“What we knew from earlier was that the immune system could be restored, but we weren’t clear on how that would be sustained over time,” Adrian Thrasher, an immunologist at the University College London involved in the research, said in a telephone interview. “Now we know it is sustained, and the long-term recovery appears to be comparable to conventional transplant.”
In gene therapy, scientists replace non-functioning genes with normal ones using a carrier molecule such as a virus; repair abnormal DNA; or alter how the DNA works.
Use of the therapy has been controversial, and not always successful.
In 1999, 18-year-old Jesse Gelsinger died of a massive immune response within hours of being treated for a liver disease at the University of Pennsylvania in Philadelphia. That was followed in 2007 by the death of a woman who received a modified gene in an arthritis trial run by Targeted Genetics Corp., now called Amphliphi Biosciences Corp., of Seattle.
The bubble boy disorder, formally known as severe combined immunodeficiency, gained national prominence in the late 1970s after reports surfaced about how David Vetter was living in a special bubble-like structure in Texas. Vetter died in 1984, after a bone marrow transplant from his sister failed.
The research was one of two studies reported today on the disorder. In one, six children, ages 6 months to 3 years, with a version of the disease called ADA-SCID, were treated, and four responded, according to the research.
In the second study, 10 children, ages 4 months to 3.8 years with a version called SCID-X1, all responded. One of the children developed leukemia as a result of the treatment, probably because of the virus used to deliver the new genes, said Thrasher, an author of the two studies.
The patient with leukemia was successfully treated with other therapies, the report said. The two children who didn’t respond to gene therapy may have not had enough gene-corrected bone marrow cells, according to the research.
The survival rate in both studies was 100 percent, Thrasher said. That compares to transplant from a non-sibling donor, where 70 to 80 percent of patients survive, he said. Today’s findings are similar to previous studies of gene therapy in other children with the condition.
“These approaches are having a benefit for the majority of patients, they’re leading relatively normal lives because of these treatments,” said Donald Kohn, an immunologist at the University of California Los Angeles, in an accompanying editorial.
Another round of trials will begin shortly, Kohn said. In those trials, researchers have changed the viruses used to insert the new DNA. The researchers are hoping for the same benefits with fewer risks, he said.