Two French babies who were born with a rare immune deficiency have apparently been cured by gene therapy. One year after being treated with genetically modified bone marrow cells, the babies have normal immune systems and no longer need to live in a sterile "bubble." The success is a much-needed shot in the arm to the field of gene therapy, which has recently struggled with safety concerns.
According to W. French Anderson, a gene therapy researcher at the University of Southern California, severe combined immunodeficiency (SCID) was a logical target for gene therapy. In people with SCID, the stem cells that would become T cells--one of the immune system's main lines of defense against infection--lack a crucial protein receptor that tells them to start reproducing. If a correct copy of the gene for the receptor could be inserted, the new cells should reproduce normally. Before long, Anderson hypothesized, the patient should have healthy numbers of T cells.
A team of doctors led by Alain Fischer of Hospital Necker in Paris, France, tested Anderson's idea. They withdrew bone marrow cells from the two babies when they were 8 and 11 months old. They cultured the cells in the lab for a day, then exposed them for 3 days to a virus which contained the normal gene for the receptor. Then they injected the treated stem cells, which were assumed to have incorporated the new gene into their DNA, back into the babies' bone marrow.
The babies rapidly showed signs of improvement. After a month, T cells began to show up in their blood. Shortly thereafter their T cell counts reached normal levels. And the immune cells worked: The older baby overcame a case of pneumonia that had dragged on for 9 months, and the younger baby recovered from chronic skin inflammation and diarrhea, the researchers report in the 28 April Science.
Gene therapy experts are heartened by the new results, which may counteract a wave of negative publicity after the death last year of a volunteer in a gene therapy trial at the University of Pennsylvania (ScienceNOW, 9 December 1999).
"It's as close to a definitive clinical success with gene therapy as one could have at this point in the development of the technology," says genetic engineer Richard Mulligan of Harvard University.