A Canadian success story
Although an effective vaccine against the hepatitis B virus exists, the disease remains a major health problem throughout the world. Nearly 400 million people are infected, and more than 3,000 people die of it daily. The hepatitis B virus is the leading cause of chronic liver disease , which can cause liver cirrhosis that may lead to liver cancer . Antiviral drugs are used to prevent progress to these illnesses. Unlike vaccines, which mobilize a person's immune system to fight a virus, antivirals target viral proteins directly to inhibit virus growth.
The first oral antiviral agent for hepatitis B, lamivudine , is a true Canadian success story with roots in Alberta. The research was begun in 1986 by Dr. Lorne Tyrrell and Dr. Morris Robins at the University of Alberta. Their work resulted in the discovery of several potent antivirals against hepatitis B and led to a major collaboration with Glaxo Canada (now GlaxoSmithKline ). One of the antivirals was lamivudine, a drug that had been developed for treating AIDS patients.
In 1989 Dr. Tyrrell's team showed that lamivudine is a very effective antiviral for the hepatitis B virus. Successful animal testing and human trials followed. Lamivudine is now the primary drug used to treat chronic hepatitis B carriers. It is licensed in 170 countries worldwide. "We have a lot to be proud of with this story," says Dr. Tyrrell. "Our work ushered in the era of antiviral therapy for hepatitis B."
But there is a problem with lamivudine: A very small genetic change in the hepatitis B virus renders it resistant to the drug. Newer drugs that are less prone to resistance have been developed; however, lamivudine remains widely prescribed because it is reasonably priced and very well tolerated.
"Resistance was a real disappointment, because we were hoping we had a treatment and would cure all patients of hepatitis B," says Dr. Tyrrell. "We're still working on this."
One of Dr. Tyrrell's graduate students is taking a unique approach to eliminating the hepatitis B (HBV) infection. Kim Zimmerman, who is supported by an AHFMR Studentship , is studying one of the forms that HBV takes in liver cells. While antivirals tend to be effective at getting rid of HBV in the fluid that fills the liver cells, they don't work for HBV in the nucleus of the cells.
Dr. Tyrrell also collaborated with University of Alberta colleagues Dr. Norm Kneteman and Heritage Clinical Fellow Dr. David Mercer to develop the first non-primate animal model for hepatitis C research. The three scientists have formed a company, KMT Hepatech Inc. , to do contract research work using this model. They were recently awarded a contract from the US National Institutes of Health to help independent researchers test antivirals.