A team of University of Alberta researchers has successfully created a mouse model that scientists can now use to test antiviral therapies against Hepatitis C, a contagious viral disease that usually leads to serious, permanent liver damage. The disease afflicts about 175 million around the world.
"This is certainly a major advance in the fight against the disease," says Dr. David Mercer, the lead author of the scientific paper published in this month's Nature Medicine journal. "We now have a viable way of testing new drugs which might ultimately help lead to development of a cure."
"The development of effective therapeutic strategies has been significantly hampered for more than a decade by difficulties in establishing in vitro and in vivo models of viral replication," says principal investigator Dr. Norman Kneteman, a professor of surgery at the U of A. "We've solved that problem."
Essentially, the researchers have transplanted human liver cells into a genetically-modified mouse; the transplanted cells then begin rapidly dividing and fill up much of the mouse liver. These "chimeric" mice can be infected with the hepatitis C virus, whereas previously only humans and chimpanzees have been susceptible to hepatitis C.
"Not only does the new mouse model give researchers the ability to test new therapies," says co-principal investigator Dr. Lorne Tyrrell, "it also allows researchers to study questions hitherto impossible to study, such as how the virus infects healthy cells and how the virus replicates."
"This advance opens the floodgates on basic and applied research," says Dr. Tyrrell, whose previous work on the hepatitis B virus led to the development of a revolutionary new drug proven to be an effective treatment for Hepatitis B.
Hepatitis C affects an estimated 175 million people worldwide, including approximately 3 million Americans and 300,000 Canadians. Infection leads to chronic liver disease in 70 to 80 percent of patients, with 30 percent developing cirrhosis, and five to ten percent cancer of the liver.
Liver failure secondary to long-term hepatitis C infection is the number one reason for liver transplantation in North America. There is no vaccination against hepatitis C, and current treatment using combinations of interferon and ribavirin works only in a selected number of patients.
The researchers will be presenting their work at the 8th International Symposium on Hepatitis C and Related Viruses next month in Paris. Arising from this discovery, and in keeping with the vision and strategy of both the University of Alberta and the Alberta government, the investigators have founded a biotechnology spin-off company, KMTHepatech Inc., with the goal of actively working towards a cure for Hepatitis C.
Other University of Alberta researchers involved in the work include: Daniel Schiller, John Elliott, Donna Douglas, Chunhai Hao, William Addison, Karl Fisher, Thomas Churchill, and Jonathan Lakey. Aline Rinfret of the Centre de Recherche du CHUM, Hôpital Saint-Luc, Montréal, Québec, was also a co-author of the paper.
Five of the authors were supported by the Alberta Heritage Foundation for Medical Research (AHFMR) and the Canadian Institutes of Health Research (CIHR). The Edmonton Civic Employees Charitable Assistance Fund in the Department of Surgery provided initial seed money for the research. Drs. Kneteman and Tyrrell are members of a new national centre of excellence for vaccine development (CANVAC).
Journal
Nature Medicine