YEAH RIGHT ------- IF THE MYSTERY HAS BEEN SOLVED?
--------MORE OF THEIR CHEMICALS?
WHAT IS PROTEASE INHIBTOR? ANOTHER CHEMICAL?????????
By Daniel DeNoon
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
"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
"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.
"We found that SCH6 not only inhibits hepatitis
C protease, but also allows restoration of this cellular immune
response," Gale says. "We could restore the
ability of infected cells to respond to the virus, and naturally
clear the virus on its own."
There's more good news. Gale's lab worked with genotype
1. It's the most common type of hepatitis C in the U.S.
-- and the hardest kind to treat. Yet the protease inhibitor
knocked it out.
By attacking the virus and also turning on antiviral immunity,
hepatitis C protease inhibitors would have a dual action. And
there's likely a third kind of action. Protease inhibitors likely
would make current interferon treatments work better, at lower
less toxic doses. That's an exciting idea to Leslye Johnson,
PhD, chief of the enteric and hepatic diseases branch at the
National Institute of Allergy and Infectious Diseases.
"If a compound like this goes forward into clinical
trials, it has the potential for dual activities and may work
better than what's out there now," Johnson tells WebMD.
"It might also allow people to use decreased doses of interferon.
This finding opens new
possibilities that are important for drug development. What
it says for patients is that a hepatitis C protease inhibitor,
as long as it is safe and everything else, could have multiple
ways of getting rid of the virus. That is really the bottom
At least three drug companies are working on hepatitis C protease
inhibitors. Farthest along appears to be BILN 2061 from Boehringer
Ingelheim Pharma. It's already being tested in humans. The Schering-Plough
product is not yet ready for human tests, says
Schering spokesman Robert Consalvo.
Gale's findings appear in the April 17 issue of the online journal
Sciencexpress. Also appearing in the same issue is an article
by Hiscott's lab, offering new insights into how viruses trigger
a cells antiviral immune response. That finding may lead to
effective not only against hepatitis C, but all viruses.
April 17, 2003. Michael Gale Jr., PhD, University of Texas Southwestern
Medical Center, Dallas. Leslye Johnson, PhD, chief, enteric
and hepatic diseases branch, National Institute of Allergy and
Infectious Diseases. Robert Consalvo, director of external communications,
I sure hope they are right but, in 1984 researchers were
confident that they could control AIDS with Lipoic Acid because
in a test tube lipoic acid kills the AIDS virus.
It does not work in humans.
I think we are going to be waiting for a while for this to