Gene therapy researchers at the Children’s Hospital of Philadelphia and Stanford University Medical Center in California reported encouraging early results in a trial designed to treat hemophilia B—a boost for a field that has been troubled by questions over the reporting of deaths and adverse events.
In a study published in Nature Genetics (2000;24:257–261), 3 adult patients who received low doses of the gene that codes for the production of factor IX showed evidence that the gene had been transferred into muscle. There were no adverse side effects according to Katherine A. High, MD, director of hematology research at the Children’s Hospital of Philadelphia and leader of the team of researchers reporting the results.
The gene therapy trial used an adeno-associated virus (AAV) to carry the gene into the cells. This is the first time an AAV vector has been inserted into human skeletal muscles. Researchers said that during the first 100 days after the gene therapy, 2 of the patients required less infused clotting factor.
Patients have severe hemophilia when they cannot produce ≥1% of the normal levels of clotting factor. In this study, a very low dose of the vector resulted in levels >1 percent, which is a result researchers had not expected. “This is better than we predicted based on our animal studies, and it may suggest that this gene therapy is more efficient in humans than in other species,” said Dr High.
The AAV was engineered from a human virus to which most people are exposed during childhood. It is not known to cause disease. This particular vector was manufactured by Avigen, Inc, whose scientists participated in the study.
The first 3 patients represent those in the low-dose group. Another 2 patients have been entered into the intermediate-dose group, and scientists anticipate adding another patient to that group and entering 3 patients in a high-dose group. “Our goal is to identify a dose in which all the patients produce levels of factor IX above 1%,” said Catherine S. Manno, MD, a hematologist at the Philadelphia hospital and the principal investigator of the clinical trial there. “This could change their hemophilia to a milder form and make a real difference in their lives.”
- Copyright © 2000 by American Heart Association