Gene therapy that corrected an inherited immune system disease in two French children also activated a cancer-causing gene in the youngsters, leading to leukemia, according to a new study.
The incident last year led to the suspension of some gene therapy studies in the United States and prompted an international team of scientists to analyze the cases to find out what went wrong.
In a study appearing Friday in the journal Science, the researchers concluded that genetically manipulated bone marrow cells injected into the two young patients somehow turned on a cancer-causing gene called LMO2. This, in turn, caused the patients to develop leukemia.
The patients were among a group of 11 boys born with a severe form of immune deficiency who were successfully treated using gene therapy by Dr. Alain Fischer, a Paris medical scientist. They were the only two to develop leukemia from the therapy, but that was enough to cause U.S. medical officials to suspend 27 gene therapy studies.
All 11 of the boys inherited a disorder called severe combined immune deficiency. Patients with this disorder have virtually no defenses against germs. Most such patients must live in a sterile environment until the inherited condition is corrected. The disorder is often called the “bubble boy disease” because a well-known Houston victim, known only as David, lived for years in a plastic bubble filled with filtered air. About one in 50,000 babies are born with SCIDS.
The condition can be treated with an injection of compatible bone marrow, which will make the missing immune system factors and provide patients with protection from infection. This is frequently not possible because doctors are unable to find a matching bone marrow for transplantation.
Fischer successfully treated his patients with a technique that restored the immune system genes that the boys lacked. The doctor did this by removing some of the boys’ bone marrow and inserting the missing genes into these blood-making cells. The bone marrow was then returned to the patients where the genetically manipulated cells made the normal complement of immune system factors to provide normal protection from infection.
In the two boys who got leukemia, the researchers found that the manipulated cells also turned on a gene that caused the disease.
The leukemia in the two boys was treated with chemotherapy and bone marrow transplants. Both patients are now in remission and considered healthy, the researchers report.