Doctors use gene therapy to fix 'bubble boy' disease

Relying on the trickery used by HIV to infect people, doctors at two medical centres say they have cured 10 infants of so-called bubble boy disease, a genetic defect that leaves children, typically boys, without an immune system.

The technique replaces a defective version of a gene the body needs to build cells that seek out and destroy invading germs. Earlier versions of the treatment have been less efficient and also posed a risk of triggering leukemia.

The doctors said they have skirted the leukemia problem by implanting "insulators" around the replaced gene, preventing the treatment from accidentally activating adjacent genes and causing cancer.

Three months after treatment, non-defective immune cells appeared in all but one of the treated children. That child was successfully treated with a second round of gene therapy 12 months after his initial therapy.

All have normal growth and development, and any infections they had suffered because of their disabled immune system have disappeared. There have been no signs of leukemia.

"The kids are cured because for the first time we are able to restore all three types of cells that constitute a full immune system," lead author Dr. Ewelina Mamcarz of the bone marrow transplantation and cellular therapy center at St. Jude Children's Research Hospital in Memphis, Tennessee, said at a news conference. "Our patients are able to generate a healthy, fully-functional immune system and are now responding to vaccinations, and that's a first for a gene therapy trial."

Results from the first eight babies treated at St. Jude and the University of California, San Francisco Benioff Children's Hospital through September 30 appear in the New England Journal of Medicine.

Those children, treated when they were 2 to 14 months old, have only been followed for 7 to 25 months, so further study will be needed to determine if there are any long-term problems.

The 10th child is due to be released from the hospital this week, about four months after treatment. It typically takes three or four months for the corrected cells to sufficiently build up the immune system to allow a child to leave isolation.

He's like a normal, healthy baby.- Kristen Simpson

Based on the results so far, said St. Jude president Dr. James Downing, "we're comfortable at this point stating this is cure."

"Only time will say if this is a durable lifelong cure," said Dr. Alain Fischer, a professor at the College of France who is also with the Unit of Pediatric Immunology, Hematology and Rheumatology at Necker Hospital for Sick Children in Paris. He was not involved in the new treatment, but helped develop an initial gene therapy for the condition 20 years ago.

The new work "is a significant step forward in the development of gene therapy and specifically for these diseases," Fischer told Reuters Health in a telephone interview.

Earlier treatments were less efficient and less safe, although the first patient Fischer's team treated remains alive 20 years later and is still doing well.

Bubble boy disease, formally known as X-linked severe combined immunodeficiency or SCID-X1, is a rare genetic defect that leaves the baby defenseless against infection. Treatment usually requires getting stem cells from a donor, which can be dangerous if the donor isn't a closely-matched brother or sister. Sibling donors are usually available in fewer than 20 per cent of cases.

The disease drew headlines in the 1970s with the case of David Vetter, who grew up cocooned in plastic. His story inspired the 1976 John Travolta movie The Boy In the Plastic Bubble.

Other genetic disorders 'amenable to this approach'

The new technique, developed at St. Jude, involves taking some of the baby's bone marrow and using an HIV-type virus to inject a working copy of a gene known as IL2RG into cells. The gene makes a protein essential to building a properly-functioning immune system. The treatment cannot cause AIDS.

Omarion Jordan, who turns 1 later this month, had the therapy in December to treat SCID.  
 
"For a long time we didn't know what was wrong with him. He just kept getting these infections," said his mother, Kristin Simpson. Learning that he had SCID "was just heartbreaking ... I didn't know what was going to happen to him."
 
Omarion now has a normal immune system. "He's like a normal, healthy baby," Simpson said. "I think it's amazing."

Omarion is the 10th boy treated in the study, which is ongoing. It's sponsored by the American Lebanese Syrian Associated Charities, the California Institute of Regenerative Medicine, the Assisi Foundation of Memphis and the U.S. federal government.

Rights to it have been licensed by St. Jude to Mustang Bio. Doctors say they have no estimate on what it might cost if it does become an approved treatment. They say they also hope to try it for more common problems such as sickle cell disease. 

Mamcarz noted that "any genetic disorder with a known genetic defect is amenable to this approach."

Some previous attempts to cure bubble boy disease have only produced temporary results. She said this treatment doesn't seem to have that problem.

"In previous trials, waning of the immune system was observed much, much earlier — within the first year," Mamcarz said. One patient treated with the new technique has been followed for more than two and a half years with no sign that the benefits are fading.