After a year of scant progress in the once-promising field of gene therapy, German scientists said Sunday that they had successfully used the experimental technique to cure two patients with a rare immune disorder.
The patients suffered from chronic granulomatous disease, or CGD, an inherited illness that leaves its victims susceptible to life-threatening infections.
The disease, which affects about 1,500 people in the U.S., is caused by a defect in a gene needed to destroy harmful bacteria. Few patients survive into middle age.
Since the German patients received the therapy 18 months ago, they have been free of bacterial and fungal infections, according to a study published online by the journal Nature Medicine.
“Everyone in the field had crossed their fingers and had high hopes there would be a clinical benefit,” said Dr. Harry L. Malech, head of genetic immunology at the National Institute of Allergy and Infectious Diseases, who was not involved in the study. “This is an important proof of principle.”
The success comes one year after three children in a French gene therapy experiment developed leukemia and one died. The setback cast a pall over gene therapy research and led authorities in the U.S. to temporarily suspend 27 clinical trials.
Scientists said they hoped the German study would help restore faith in a promising technology.
“A new disease has been cured by gene therapy,” said Dr. Donald Kohn of Childrens Hospital Los Angeles, who was not involved in the research. “Gene therapy is making progress.”
Scientists started researching gene therapy more than a decade ago to treat genetic diseases, such as sickle cell anemia and cystic fibrosis. They believed that giving patients a healthy gene would not merely treat their symptoms but would cure their disease.
The process involves using a virus to insert the new gene into a patient’s cells.
A major success of gene therapy was curing a group of French children of a rare disease known as severe combined immunodeficiency disease.
But the breakthrough turned into one of its biggest setbacks when some of the children developed leukemia. Scientists believe the corrected gene inadvertently activated a nearby gene that sparked the cancer.
In the latest study, a group led by Manuel Grez of the Institute for Biomedical Research in Frankfurt put a healthy version of the CGD gene into a modified mouse leukemia virus.
The virus was then used to insert the gene into white blood cells called neutrophils that had been removed from each patient.
Before returning the cells to the patients, researchers destroyed some of the defective immune cells with a low dose of chemotherapy.
Scientists said that within 50 days of receiving the infusion, about 20% of the patients’ neutrophils were the healthy version. That surprised researchers because just 5% was needed to cure the disease.
Before the trial, the patients had required frequent infusions of antibiotics to keep chronic infections at bay. One patient, a 26-year-old man, had a long-lasting liver abscess. The second patient was a 25-year-old man with a chronic lung infection.
After gene therapy, those infections cleared, Grez said. He was optimistic about the future of the treatments, saying “our study may open the way to treat several other diseases of the blood.”
But the speedy proliferation of neutrophils has raised some concerns. The study reported that the cells continued to reproduce rapidly, eventually making up 60% of the patients’ bacteria-fighting white blood cells.
The rapid reproduction, if unchecked, could lead to leukemia.
The growth was “very dramatic,” said Dr. Mary C. Dinauer of Indiana University School of Medicine, who was not involved in the research. “People have concerns. You can get too much of a good thing.”
Dr. Christof von Kalle, a researcher from the German Cancer Research Center and a coauthor of the German study, said that patients were being closely monitored and that there had been no signs of cancer.
He said the corrected cells seemed to have stopped their encroachment. Scientists said it could take several years to find out whether cancer would develop in the patients.