Oct. 11, 2006 A major finding that could lead to a new approach for treating hepatitis C and other chronic virus infections was announced today by researchers at the La Jolla Institute for Allergy & Immunology (LIAI). The research team, using controlled laboratory studies of mice, was able to eliminate a chronic virus infection in the animals by blocking a key messenger molecule in the immune system. The finding has particular relevance for hepatitis C, a viral illness which can cause liver disease and cancer, but may also be applicable to AIDS, cytomegalovirus and other chronic virus infections.
"This is a significant advance that holds great promise for the treatment of chronic virus infections," said Mitchell Kronenberg, LIAI President & Scientific Director. He noted that the research is particularly exciting because the scientific team was able to completely eradicate the usually chronic infection in the mice, not just tone it down, like many of the current treatment methods for such infections.
The research team, led by Matthias von Herrath, M.D., announced its finding in a paper, "Resolution of a Chronic Viral Infection Following IL-10 Receptor Blockade," published today in the online version of the Journal of Experimental Medicine. A separate study, led by Michael Oldstone from the Scripps Research Institute, produced similar results and was published Sunday in a science journal.
LIAI's research team used a novel method for tackling a chronic viral infection, which involved releasing the disease-fighting power of the immune system by blocking the interleukin-10 (IL-10) messenger molecule receptor with a simple antibody. Normally, this molecule, which is produced at substantial levels during hepatitis C, HIV and cytomegalovirus infections, acts to suppress the immune system's attack on chronic virus infections. "We thought, 'what if we try to correct what the immune system seems to be doing wrong in response to many chronic viral infections?,'" said von Herrath. "So we unleashed the power of the immune system by using an antibody to block the IL-10 receptor. This taught the immune system to take the right action and fight the disease."
The discovery by scientific researchers that mice chronically infected with lymphocytic choriomeningitis virus produce large amounts of IL-10 led to the development of this new intervention. Von Herrath used a version of the virus that causes chronic infections in a study involving 40 infected mice. The mice were treated with the IL-10-blocking antibody for two weeks. "They got better after one week," he said. "After two weeks, the infection was resolved in the majority of the mice and, in the end, all animals were able to cope with the virus. They developed a normal antiviral immune response, gained weight and returned to a healthy state." Von Herrath noted that their studies showed that the treatment worked best when given immediately after infection. "The later you give it after the infection, the lesser the efficacy," he said.
Von Herrath said that future studies in humans should primarily target hepatitis C because it causes the body to produce the most IL-10 of any of the chronic virus infections. Hepatitis C has been compared to a "viral time bomb." The World Health Organization estimates that about 180 million people, some 3% of the world's population, are infected with hepatitis C virus, 130 million of whom are chronic carriers at risk of developing liver cirrhosis and/or liver cancer. The hepatitis C virus is responsible for 50--76% of all liver cancer cases, and two thirds of all liver transplants in the developed world. Current estimates in the U.S. are that 3.9 million Americans are chronically infected with hepatitis C.
Currently, hepatitis C is treated with a variety of drugs, with only modest success. "The problem is you need to strengthen the immune system to fight the (chronic) virus, but in doing so it may destroy too many cells. This cellular damage can eventually become intolerable for the body," Von Herrath explained, a condition known as immunopathology. However, in their studies with IL-10, "we found that by blocking this molecule, you can release the brakes on the immune system at a crucial juncture," he said. "This results in an immune system attack that is intense enough to rid the body of the disease, but not so high as to cause immunopathology."
Von Herrath said the research team will continue to expand on the finding. "One of the next steps will be to test the IL-10 blocking antibody on human cells in the lab to see whether these cells also become normal and functional against the virus and to test combination therapies that add viral vaccines, anti-viral drugs and other antibodies to the IL-10 receptor blockade. Combination therapies bear the promise to minimize potential side effects while achieving synergy in combating the viral disease."
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