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Hepatitis C Achilles Heel Found

Drugs Now In Pipeline May Shorten, Ease Hepatitis C Treatment
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April 17, 2003 -- The central mystery of hepatitis C now is solved. A new finding promises more effective, shorter, and easier hepatitis C treatments.

What Michael Gale Jr., PhD, and colleagues discovered is how hepatitis C virus establishes lifelong infection. They found that the virus makes a key that lets it turn off a cell's anti-virus machinery. And they found that a type of drug -- already in development by several companies -- robs the virus of this key. Without it, the anti-viral machinery comes to life. It churns out a chemical called interferon that rids the cell of the hepatitis C virus.

"The beauty of [this type of drug] is it can clear persistently infected cells," Gale tells WebMD. "The cells rid themselves of hepatitis C virus within an average time of four to five days."

Gale and colleagues at University of Texas Southwestern Medical Center, Dallas, wondered why hepatitis C virus is able to cause long-lasting infection. Most viruses can't do that. Gale guessed that hepatitis C virus must somehow disable a crucial immune response -- some part of the innate immune system that's part of almost every cell in the body.

A crucial clue came from the McGill University lab of John Hiscott, PhD, in Montreal. Hiscott was studying the molecular switches that trigger interferon release inside a cell. One of these triggers is called interferon regulatory factor 3 or IRF-3. He gave Gale some IRF-3 to work with.

Gale's lab then found that a protein made by hepatitis C virus blocks IRF-3.

"By blocking it completely, hepatitis C virus prevents the cell from mounting an immune response," Gale says. "That lets the virus get a foothold soon after infection. Once it has this foothold, it never lets go."

The IRF-3 blocking protein is an enzyme called protease. Like hepatitis C virus, the AIDS virus also makes a kind of protease. Drugs that disable protease -- protease inhibitors -- revolutionized AIDS treatment. Several inhibitors of hepatitis C protease are now in the drug pipeline. Schering-Plough Corp. gave Gale some of its experimental drug, which he calls SCH6.

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