New gene therapy treatment showing promise against 'bubble boy' disease
By Gene Emery NEW YORK (Reuters Health) - More than a decade ago, doctors showed dramatic progress in helping infants born with a severe deficiency in their immune systems, a condition known as "bubble boy" disease. But when one quarter of treated children developed leukemia within two to five years, researchers went back to the drawing board. Now a new variation of that therapy, which also uses a genetically-engineered virus to help the body create disease-fighting T-cells, is showing similar early promise, and none of the children who have received the therapy have show any evidence of cancer, according to preliminary results reported in the New England Journal of Medicine. "It's clear that this virus is effective. It does correct the T-cell defect in these patients as well as the last one did," coauthor Dr. David A. Williams, chairman of hematology/oncology at Boston Children's Hospital, told Reuters Health. "We can't say yet there will be no leukemias. In fact, we will follow these children for 15 years altogether," he said. But he characterized the interim results as "encouraging." The rare condition is officially called X-linked severe combined immunodeficiency syndrome. It gets its "bubble boy" nickname because its victims are only safe in a sterile environment. The genetic defect leaves the boys - whose single X chromosome makes them targets of the disease - unable to fight infection. In the outside world, they usually die within a year. The therapy involves removing bone marrow cells from patients, selecting specific cells that build the immune system and exposing those cells to the genetically engineered virus. Initially, the cells lack the genetic code for building a healthy immune system. The virus is trained to insert that missing code. The reprogrammed cells are then infused back in the child. The earlier virus apparently activated chunks of the genetic code that can lead to leukemia. Doctors hope the new virus won't do that. They note that in the current study, the new delivery-vehicle virus did not tend to insert near the cancer-causing genes as the original virus had. The New England Journal study reports on the first nine children treated with the new virus. The boys were all between four and 10.5 months old when they received the gene therapy. Of the eight boys still alive, the treatment rebuilt the immune systems of seven. In six of those seven cases, the counts of disease-fighting T cells in the blood rose to normal levels, and those cells were found to be able to actively fight disease. In the seventh case, the response wasn't as strong; the child was re-treated and his T cell count remained low, although he is healthy. In the eighth case, the treatment failed to rebuild the immune system, but the child has survived thanks to a successful stem cell transplant. Such transplants can be risky without a matching donor, but they are the best therapy available. In none of the eight cases has leukemia developed. However, the children have only been followed for 16 to 43 months. A ninth child enrolled in the study died four months after treatment from an infection he had been fighting at the time gene therapy treatment began. "The data suggest this vector system is safe, and could be used for other disease," said Williams, who is also a pediatric oncologist at the Dana-Farber Cancer Institute in Boston. Five of the children were treated in France; four in the United States. SOURCE: http://bit.ly/1rcG9rh New England Journal of Medicine, online October 8, 2014.
