Gene therapy has reversed a dangerous immune disease in two babies, keeping them healthy for nearly a year so far. In a third child, treated 4 months ago, the therapy also appears to be working, researchers in France report. The babies no longer need to be kept in isolation.
The findings, described in the April 28 Science, come at a time when gene therapy is under fire in the United States. The Food and Drug Administration terminated one study in which a teenage boy died. Other gene-therapy trials deemed to pose health risks have been suspended, casting doubt on the technology’s future in this country.
Although including only three patients and fighting a disease that’s rare, the new study may put to rest the frequent criticism that gene therapy hasn’t cured anyone, says Alan W. Flake, a pediatric surgeon at Children’s Hospital in Philadelphia. “It’s a landmark paper in that it’s the first clear-cut, demonstrated treatment with gene therapy—of any disease that I know of—that’s persisted for a significant length of time.”
The gene therapy in the French trial corrects an inherited mutation on the X chromosome that leaves children unable to make essential cell-surface proteins. The molecules are necessary for manufacture of immune T cells and natural killer cells—two of the body’s staunchest defenders against disease.
The scientists took bone marrow from the babies—who were 1, 8, and 11 months old—and identified cells capable of developing into immune cells. They incubated these precursors in the laboratory with a retrovirus engineered to deliver intact genes encoding the missing proteins.
After 3 days, the researchers injected each baby with its own genetically altered marrow cells. These then developed into thriving T cells and natural killer cells, reports study coauthor Alain Fischer, an immunologist at Necker Hospital in Paris.
Babies born with this condition, severe combined immunodeficiency, typically receive a bone marrow transplant from a donor. The children must then wait months in seclusion for new immune cells to proliferate from the transplant. The original “boy in the bubble” survived for years with this disease in extraordinary isolation, although now patients usually just stay in separate hospital rooms, visited only by people wearing gowns and masks.
The transplants are most successful when a perfectly matched donor is found. But that’s rare, and children with poor matches usually require monthly immune-boosting shots indefinitely.
Despite this drawback, bone marrow transplant is likely for now to remain the treatment of choice in such children, says Elaine S. Collier, an immunologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. The gene-therapy technique is exciting but cumbersome, she says. “Manipulating cells outside [the body] is tougher than just putting cells in,” she says.
The researchers lifted the isolation precautions for each baby 3 months after gene therapy. All three children are now at home, without medication or side effects, Fischer reports.