Release date: Oct. 30, 2002
Emory Researchers Seek Effective Treatment for Hepatitis C
Two Emory University researchers who are behind a recent, significant breakthrough in AIDS therapy now have their sights set on a new target: Finding a treatment for hepatitis C, a disease affecting 3.9 million Americans. Known as the "silent epidemic," hepatitis C affects one out of every 50 Americans.
For 15 years, Emory chemist Dennis Liotta and his research partner Raymond Schinazi, an Emory School of Medicine professor and director of Emoryís laboratory of biochemical pharmacology based at the Atlanta Veterans Affairs Medical Center, have worked to unravel the mystery of HIV and develop viable treatments for it. They now face a potentially more difficult challenge in finding a treatment for hepatitis C.
"Hepatitis C is a very tough problem. Literally millions of different small molecules have been screened, but none of them work on hepatitis C," Liotta says. With no vaccine available, treatments such as interferon help some sufferers to live with the disease, although the side-effects can be harsh and the treatments do not work for everyone, according to Liotta. However, recently modified forms of interferon, when combined with the drug ribavirin (which enhances the immune system), have been an improvement for some patients, he says.
In the United States, hepatitis C is the number one cause of chronic liver disease and is the direct cause of death for about 10,000 people a year. About two percent of the countryís population is infected with the hepatitis C virus (HCV), and of those, about 80 percent develop chronic liver diseases such as cancer and cirrhosis. Many people do not realize they have hepatitis C until they begin experiencing symptoms of chronic liver disease and failure 20 or 30 years after they were originally infected. In other nations, the infection rate is in the double-digits, up to 25 percent in some areas. Worldwide, about 200 million people are infected with HCV.
Liotta and Schinazi want to find a way to halt the replication of HCV. To do so, their goal is to design a chemical compound that will mimic the nucleotides (the chemical building blocks of RNA and DNA) of the virusí genes. With this "false" nucleotide in place, the virus will not be able to reproduce. Once the virus is stopped, the cells carrying the virus eventually die and clear from the body. As a result, a person with the virus can be freed of the disease.
"The house will crumble by putting in an erroneous building block in the gene of the virus as it tries to grow. Itís like throwing a wrench in the works to shut down the virus machinery and keep it from reproducing," says Schinazi.
Liotta and Schinazi say it is difficult to speculate when a drug to treat HCV could be on the market. At this point, they are designing and testing nucleotides at the cell level. If they get a "hit," the compound would be refined and tested for toxicity, and could then potentially move on to drug trials, Liotta says.
HCV is a one of a special set of viruses, called RNA viruses, which can out-maneuver the human immune system. They do this by mutating and reproducing rapidly, often evolving faster than the immune system can develop an effective response to them. Despite its "sneakiness," it is a curable disease, Schinazi and Liotta emphasize, since HCV fortunately doesnít integrate into the host DNA genome and become a permanent part of the genetic code.
"The nucleotides of HCV are particularly difficult to mimic, which has made finding a treatment for it such a challenge for researchers around the world. Itís the area of virology where everyone is pushing as hard as they can to find a solution," says Liotta.
Liotta and Schinazi plan to continue to work on treatments for HIV as that virus continues to evolve, but hepatitis C has moved to the forefront of their focus. "It is a natural progression of our work. It is one of the last frontiers for those of us involved in viral chemotherapy," says Schinazi.
While they pursue HCV, the two researchers also are awaiting approval by the Food and Drug Administration for the anti-HIV medication FTC, a compound they discovered known as emtricitabine. FTC is being further developed and will be marketed and commercialized by Triangle Pharmaceuticals under the brand name Coviracil. If approved, the drug "potentially will revolutionize the treatment of AIDS by providing a safe and potent once-a-day oral treatment that will expand the treatment options for HIV-infected individuals," Liotta says.
Liotta and Schinazi previously developed the drug lamivudine that is marketed by GlaxoSmithKline under the brand name Epivir by itself, and Combivir when combined with the longtime AIDS drug AZT. Lamivudine is used in a majority of HIV "drug cocktail" treatments.