Re: [GIWorld-Hepatitis] FW: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C
- This is looking like it might work.........Yea Team!!!! How are you doing? I'm hanging in. Just went to doc.......no change........so we're in a holding pattern. Added the flax seed back to the works. Thanks for the reminder.
Hang in there, girl!
>From: alleypat <alleypat@...>
>Sent: Feb 21, 2006 5:36 PM
>To: firstname.lastname@example.org, GI World-Hepatitis <GIWorld-Hepatitis@yahoogroups.com>
>Subject: [GIWorld-Hepatitis] FW: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C
>"If the doctor told me I had six minutes to live, I'd type a little
>faster." --Isaac Asimov
>From: nataphcv-bounces@... [mailto:nataphcv-bounces@...]On
>Behalf Of nataphcv@...
>Sent: Tuesday, February 21, 2006 6:31 AM
>To: nataphcv@...; nataphcvhiv@...; natapindustry@...;
>Subject: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C
>Hep C Protease Inhibitor: Waging War on Hepatitis C
>FEBRUARY 21, 2006
>By John Carey
>By sleuthing out how the virus disarms the immune system, scientists could
>be closing in on a cure. Vertex Pharmaceuticals has taken the lead
>Many viruses have figured out ways to elude the body's protective system.
>One of the cleverest is the hepatitis-C virus. In scores of millions of
>infected people, the bug does its damage by making trillions of new viruses
>a day, years after year.
>The eventual result often is liver failure or cancer. The cost to the
>health-care system: an estimated $20 billion to $50 billion a year in the
>But while the virus' ability to hide from the body's defenses is well known,
>the details of its cunning strategy were a mystery -- until now. The answer
>is not only a scientific surprise; it also has important medical
>Experimental drugs now in clinical trials will be far more effective against
>the virus than anyone had expected. "The drugs have shown such a tremendous
>effect because the virus is getting a double whammy," explains Dr. Stanley
>Lemon, professor of microbiology, immunology, and internal medicine at the
>University of Texas Medical Branch at Galveston. He's one of the leaders of
>the effort to decipher the mechanism.
>ALARMING DISCOVERY. Here's why. Like most viruses, the hepatitis-C bug
>commandeers the host's cellular machinery to make copies of itself. For
>instance, it uses cells' protein factories to make proteins that will become
>the virus' coat. But before these proteins can be assembled into the coat,
>they must be sliced and diced in several key places. That's the job of a
>viral enzyme called protease.
>When Lemon and his colleagues set out to learn how hepatitis C evaded the
>body's defenses, they discovered that the enzyme was doing another,
>unexpected, job. "It was a surprise to find that the protease of the virus
>was involved in blocking the innate immune system response," he says.
>Lemon's team employed some elegant scientific sleuthing to solve the
>mystery. Turns out that "the protease targets two cellular signaling
>molecules at the very beginning of the immune process," he says.
>Think of the immune system as having a built-in burglar alarm. Cells roam
>the body equipped with little detectors, or receptors, on their surface.
>These receptors seek out and attach to foreign invaders, such as viruses.
>Once the receptor finds such an invader, it sends out an alarm, mobilizing
>the immune system to attack the invader.
>In the case of the hepatitis-C virus, the cells successfully identify them
>as foreign invaders. But the alarm signal they try to send doesn't get
>through. The viral protease, Lemon discovered, chops up two crucial
>molecules that carry the alarm. So even though the "burglar" is detected,
>the alarm never gets sent to the immune system's police station.
>ONE LOCK, MULTIPLE KEYS. This ability to evade the immune system has two
>enormous consequences for drug development. First, a drug that successfully
>targets the viral protease will be unusually effective. That's because it
>would not only hit the virus directly, but would also restore the immune
>system, which is then able to launch its own attack.
>But such drugs are difficult to design. That's a direct result of the viral
>protease enzyme's unusual ability to have several targets -- the viral
>proteins it cleaves to ensure viral reproduction, and the immune system
>Most enzymes work only on one target. When scientists look at their
>three-dimensional shape, these normal enzymes typically have a deep
>indentation or pocket. The target protein fits into that pocket like a key
>into a lock.
>The hepatitis-C protease enzyme, however, has figured out how to work on
>several targets. "There are multiple keys for that one lock," explains
>Lemon. As a result, the lock -- that is, the pocket -- must be exceptionally
>HUGE PAYOFF POTENTIAL. Indeed, when scientists at Vertex Pharmaceuticals
>(VRTX ) in Cambridge, Mass., figured out the shape of the enzyme in 1997,
>they discovered that it has an unusually shallow pocket. That, in turn, made
>it hard to design a drug that fits in the "lock." When the shape of the
>enzyme was discovered, "we said: 'Oh, boy, that will be a tough problem,'"
>recalls Vertex Chief Executive Josh Bogor.
>It took the company years to design a drug that could fit in the pocket,
>thus disabling the viral enzyme. "It turned out to be an excruciating,
>atom-by-atom exercise," says Boger.
>The potential payoff, however, is huge. Results of a small trial with the
>drug, announced by Vertex in early February, were astonishing. After four
>weeks of treatment with the drug, in combination with the current standard
>treatment, the hepatitis-C virus became undetectable in all of the 12
>The hope, of course, is that the drug's dual effect -- attacking the virus
>and restoring the immune system response -- will bring an actual cure for
>patients infected with the virus. That would be a major advance from current
>treatment, which uses an immune system booster called interferon, a
>treatment that is often debilitating. It takes many months to even have a
>chance of working, and fails in a large number of cases.
>UNFORESEEN SIDE EFFECTS? Vertex isn't the only company in the hunt with a
>protease inhibitor for hepatitis C. Schering-Plough
>(SGP) has one in Phase II clinical trials, and on Jan. 30 reported that it
>had gotten fast-track designation from the FDA. GlaxoSmithKline (GSK ) is
>said to be working on one as well. Boehringer Ingelheim was actually in the
>lead at one point, but it had to stop development of its promising candidate
>because of side effects.
>Another possible stumbling block: The new Vertex drug could still fail in
>upcoming trials, due to unforeseen side effects. But based on the latest
>results, it is currently the best hope. Wall Street has taken notice. Vertex
>shares now cost around $38, up from $8.83 last April.
>This tale may be a rare case of a drug working far better than anyone
>expected -- all thanks to the hepatitis-C virus' remarkable ability to shut
>off the immune system.
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