Bubble Boy Disease a Gene Therapy Success Story?

April 17, 2002; Paris, FRANCE (AP) -- In the most striking success yet for gene therapy, French doctors have apparently cured four little boys of the rare and deadly immune system disorder dubbed "bubble boy disease." The boys, followed for up to 2-1/2 years, now have healthy immune systems, are growing normally and live at home after spending their first months in a sterile environment because they could not fight off disease. The immune system of a fifth boy was partially restored and he is improving with other treatment.

The doctors two years ago reported initial success with the first two patients; the update in Thursday's New England Journal of Medicine shows the treatment is still working. :"This is the first instance in which an otherwise fatal disease has been treated with gene therapy as the only treatment and the disease was reversed," said Dr. Jennifer M. Puck, head of the Immunologic Genetics Section at the National Human Genome Research Institute. "This is exciting, and it's important." The gene therapy was given to the boys in 1999 and 2000 when they were babies; the youngest was one month old, the oldest was eleven months. The oldest of the boys is now about four years.

Puck, who was not involved in the research, said scientists are getting better at gene therapy experiments, but so far patients treated for other disorders still need regular, expensive medication to survive. The study is welcome news for the gene therapy field, which suffered a setback when an experiment killed a teenager at the University of Pennsylvania in 1999. The death raised fears that the experiments might be too dangerous and led to efforts to increase safety.

The five French boys were born with Severe Combined Immuno Deficiency, or SCID, an inherited disease that occurs in about 1:75,000 births. The best-known victim was David, Houston's famous "bubble boy," who lived in a germ-proof plastic enclosure until his death at age 12 in 1984.

The French boys had "X-linked" SCID, a severe form that strikes only boys. It is the most common form of SCID, accounting for about half the cases. The boys lacked a crucial protein because of a genetic mutation. As a result, they could not make two types of crucial infection-fighting immune cells, and furthermore, a third type did not work, leaving their bodies open to infection.

Many babies with the disorder are now saved with bone marrow transplants, but they need monthly intravenous infusions of immune globulin, antibodies culled from donated blood, for the rest of their lives. To reverse the gene defect, doctors at Necker Hospital in Paris drew bone marrow from the boys. They culled stem cells from the marrow and infected them with a harmless virus in which a gene that makes the missing protein had been inserted. After the virus infected the bone marrow cells, millions of each boy's cells were injected into his bloodstream. Repeated tests showed the boys' bone marrow cells continue to make the immune cells they once lacked. In addition, they have gotten inoculated against some childhood diseases -- shots that once would have killed them.

Sonia Skarlatos, Gene Therapy Coordinator at the National Heart, Lung, and Blood Institute, said "the results do not prove the boys' immune systems have been permanently repaired, but it is the longest-lived success in gene therapy so far." "Some of the boys' stem cells still have the defective gene, but enough have the normal one to give them a good immune system," she said.

Skarlatos said the approach could eventually help cure some other genetic diseases, starting with Hemophilia and another form of SCID. "In the next five years or so, I would expect to see some results," she said.