CHAPEL HILL, N.C. - New results from gene therapy studies at the University of North Carolina at Chapel Hill may lead to an effective long-term treatment, if not a cure, for hemophilia A, the most common form of this inherited blood disease.
Studies in mice involved attaching a cloned gene responsible for human clotting factor VIII - a protein severely deficient in people with hemophilia A - to a genetically engineered virus called AAV. A single injection of the virus led to a gradual increase in blood levels of factor VIII, which have remained stable for 11 months.
"This is the first result in animals demonstrating the efficacy of this approach to hemophilia A," says Dr. Christopher E. Walsh, assistant professor of medicine at UNC-CH School of Medicine and clinical director of the university's Gene Therapy Center. "The goal is one dose -- that essentially one dose delivered by gene therapy would be all that's needed to be physiologically cured of future bleeds."
On June 9, in Washington, D.C., Walsh and his colleague, Dr. Hengjun Chao, a postdoctoral researcher at the center, will present the new findings to the American Society of Gene Therapy.
The UNC-CH researchers point out that earlier gene transfer attempts in mice using other virus systems resulted in higher blood levels of factor VIII. These, however, proved short-lived, lasting from just a few days to a few months. Moreover, those treatments proved highly toxic to the liver, which is the source of the clotting factor.
"Compared with other viral vectors - retrovirus and adenovirus - AAV has its advantages: it is nonpathogenic, non-toxic, and provides very long-term expression of the factor VIII protein," Chao says.
The UNC-CH researchers were able to achieve factor VIII levels up to 20 percent of normal in a strain of healthy mice and factor VIII "knockout mice," a strain genetically bred without the gene for the clotting protein.
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Contact: Lynn Wooten
LWooten@unch.unc.edu
919-966-6046
University of North Carolina School of Medicine
9-Jun-1999