They used the drug to block the receptor before, during and after inoculation with the virus, in cell culture and in a small-animal model, to evaluate the receptor's role in infection and the drug's potential as an anti-hepatitis agent.
The researchers showed that ezetimibe inhibited HCV infection in cell culture and in mice transplanted with human liver cells. And, unlike any currently available drugs, ezetimibe was able to inhibit infection by all six types of HCV.
The study, Uprichard said, opens up a number of possibilities for therapeutics.
Hepatitis C is the leading cause for liver transplantation in the U.S., but infected patients have problems after transplant because the virus attacks the new liver, Uprichard said.
While current drugs are highly toxic and often cannot be tolerated by transplant patients taking immunosuppressant drugs, ezetimibe is quite safe and has been used long-term without harm by people to control their cholesterol, Uprichard said. Because it prevents entry of the virus into cells, ezetimibe may help protect the new liver from infection.
For patients with chronic hepatitis C, ezetimibe may be able to be used in combination with current drugs.
"We forsee future HCV therapy as a drug-cocktail approach, like that used against AIDS," Uprichard said. "Based on cell culture and mouse model data, we expect ezetimibe, an entry inhibitor, may have tremendous synergy with current anti-HCV drugs resulting in an improvement in the effectiveness of treatment."
|Contact: Jeanne Galatzer-Levy|
University of Illinois at Chicago