Gene therapy tests stopped after cancer case

On Tuesday the U.S. Food and Drug Administration said it was stopping about 30 gene therapy trials after discovering that a second child in a French gene therapy experiment has leukemia.

In France two boys were diagnosed with leukemia after receiving the experimental treatment for ‘bubble boy disease’ — X-linked severe combined immunodeficiency, or SCID. A genetic defect leaves such children (always boys) without an immune system. Without treatment, these children can die of infections that would barely affect a healthy child. The gene therapy is used to reinforce the children’s bone marrow using genetically engineered immune cells. The therapy had worked extremely well in these children. They were among 10 gene therapy patients in France who were living normal lives before the leukemia symptoms began. Both leukemia patients are apparently being helped by chemotherapy, said Dr. Philip Noguchi, head of gene therapy issues at the FDA. ‘We do know that both children, the first one and second one, are clinically stable,’ he told Reuters. The French researchers, led by Dr. Alain Fischer of Necker Hospital in Paris, declined to comment, saying they would need to notify the parents of all their patients first. In September 2002 after the first boy in France was diagnosed with leukemia the FDA suspended three similar gene therapy trials in the United States. British regulators declined to suspend similar experiments there. The FDA told scientists those suspensions will hold until the leukemia cases are checked out. As a precaution, they have added just fewer than 30 trials that also used retroviruses to target bone marrow stem cells, Noguchi said. Gene therapy uses a vector (usually but not always a virus) to carry a healthy gene into the cells of patients. When it works correctly, the virus injects its DNA and the new gene into cells and corrects the genetic defect. In October, scientists said the retrovirus in the French experiments might have injected its DNA into a vulnerable site in a single blood cell. This may have caused damage that would cause that cell to proliferate, causing the leukemia. The FDA is reviewing 150 gene therapy trials that used a retrovirus as a vector. Noguchi said since October, about 50 of those had closed down because the patients had died of their diseases, but the rest are still being reviewed. He said so far the review found no evidence anyone in a U.S. gene therapy trial had developed cancer. The question is whether the risk of cancer outweighs the risk from gene therapy, which is highly experimental but is usually a patient’s only hope. In the initial French case, the child was reported to be faring well on chemotherapy for his cancer. Leukemia in children is generally easy to treat, with cure rates of 90 percent or more. In contrast, children with SCID who cannot get a bone marrow transplant almost always die within a year. ‘I think we shouldn’t view this as the death knell to gene therapy,’ said Dr. Harry Malech of the National Institute of Allergies and Infectious Diseases, whose scheduled gene therapy trial involving X-SCID patients has been suspended. ‘We need more good science to sort out what went wrong,’ he said in a telephone interview. Noguchi said the FDA would consider allowing the most desperate patients, those who will die without treatment, to continue on gene therapy. The American Society of Gene Therapy called the suspension prudent. ‘Understanding the mechanisms that underlie the development of leukemia may lead to improved methods of gene therapy … that can minimize the risks but preserve the benefits,’ the group said in a statement.(Source: Reuters Health)