Gene therapy works for 'Bubble Boy' disease

Nine years after getting gene therapy for a rare, inherited immune system disorder often called "bubble boy disease," 14 out of 16 children are doing well, researchers report.

The children were born with severe combined immunodeficiency disease (SCID). They got an experimental gene therapy in the U.K.

A new report shows that nine years later, 14 of the 16 children had working immune systems and were leading normal lives.

"These children, who would have died very young without treatment, are participating in life as fully as their brothers and sisters," researcher H. Bobby Gaspar, MD, PhD, tells WebMD. "Most of them are going to school, playing ball, and going to parties."

Few Treatment Options for SCID

Children with SCID carry genetic defects that prevent their immune systems from working. Without treatment, most die from infection in their first two years of life.

One exception was David Vetter, a Texas boy born in 1971. Vetter lived in a specially constructed sterile plastic bubble from birth until his death at age 12. He became famous as the "bubble boy," and his story made many people aware of SCID for the first time.

For decades, the treatment has been to get transplants of blood-forming stem cells from the bone marrow of matched siblings or other donors who have healthy immune systems.

Such transplants can effectively cure the disorder. But only about one in five children with SCID have a perfectly matched donor.

Bone marrow from partially matched donors can also be used. But those mismatched transplants are much more risky. About one in three children who have them die from the procedure.

About a decade ago, researchers discovered a way to manipulate a patient's own genes to manufacture the missing part of the gene needed to make the immune system work.

Since that time, gene therapy has been used to treat dozens of children with SCID, says UCLA researcher Donald B. Kohn, MD, who did not participate in the U.K. study.

How the Children Fared

"The big picture here is that almost 10 years down the line, all of these children are alive and 14 of 16 have been able to correct their immune systems," Gaspar says. "With [mismatched] transplants, we would have lost two to four of them."

The 16 children with SCID who got the gene therapy ranged in age from 6 months to 3 years. Four of them had the ADA-deficiency type of SCID. The other kids had the X1 form of SCID. Those are the two most common types of SCID.

For most of the children, gene therapy was a success. But one boy who had the X1 form of SCID developed treatment-related leukemia. The complication was not unexpected, Gaspar says, because four children with the X1 from of SCID in a French study had developed leukemia after getting the gene therapy.

Gaspar says researchers learned from those cases and have modified the treatment in hopes of reducing the risk for patients with the X1 form of the disorder.

Kohn says gene therapy should be considered the treatment of choice for children with ADA-deficient SCID who do not have perfect bone marrow donor matches. It may prove to be a better choice for patients with perfect donor matches, too, he says.

As for the X1 form of the disease, Kohn says it remains to be seen if the new approach to gene delivery works and has less risk of leukemia.

Lessons learned from the SCID trials have spurred studies to find effective gene-based treatments for other blood cell diseases, including sickle cell anemia, Kohn notes.

"The history of gene therapy research can be summarized as, 'Two steps forward and one step back.' We retrench, we learn, and then we move forward again," he says.

"Twenty years ago, nothing was working," Kohn says. "Ten years ago, these treatments started to work, but with complications. The hope is that the next decade will bring highly effective treatments with few complications."