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FW: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C

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  • alleypat
    If the doctor told me I had six minutes to live, I d type a little faster. --Isaac Asimov ... From: nataphcv-bounces@natap.org
    Message 1 of 2 , Feb 21, 2006
    • 0 Attachment
      "If the doctor told me I had six minutes to live, I'd type a little
      faster." --Isaac Asimov

      -----Original Message-----
      From: nataphcv-bounces@... [mailto:nataphcv-bounces@...]On
      Behalf Of nataphcv@...
      Sent: Tuesday, February 21, 2006 6:31 AM
      To: nataphcv@...; nataphcvhiv@...; natapindustry@...;
      natapdoctors@...
      Subject: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C


      Hep C Protease Inhibitor: Waging War on Hepatitis C

      FEBRUARY 21, 2006

      News Analysis
      By John Carey
      Businessweek.com

      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
      U.S. alone.

      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
      implications.

      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
      signaling proteins.

      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
      versatile.

      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
      patients.

      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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      _______________________________________________


      [Non-text portions of this message have been removed]
    • avansi7465
      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
      Message 2 of 2 , Mar 2, 2006
      • 0 Attachment
        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!
        Anne

        -----Original Message-----
        >From: alleypat <alleypat@...>
        >Sent: Feb 21, 2006 5:36 PM
        >To: happyheppers@yahoogroups.com, 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
        >
        >-----Original Message-----
        >From: nataphcv-bounces@... [mailto:nataphcv-bounces@...]On
        >Behalf Of nataphcv@...
        >Sent: Tuesday, February 21, 2006 6:31 AM
        >To: nataphcv@...; nataphcvhiv@...; natapindustry@...;
        >natapdoctors@...
        >Subject: NATAP: Hep C Protease Inhibitor: Waging War on Hepatitis C
        >
        >
        >Hep C Protease Inhibitor: Waging War on Hepatitis C
        >
        >FEBRUARY 21, 2006
        >
        >News Analysis
        >By John Carey
        >Businessweek.com
        >
        >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
        >U.S. alone.
        >
        >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
        >implications.
        >
        >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
        >signaling proteins.
        >
        >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
        >versatile.
        >
        >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
        >patients.
        >
        >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.
        >
        >
        > ----------
        >
        >_______________________________________________
        >NATAP nataphcv mailing list -- nataphcv@...
        >
        >This is an annoucement-only mailing list. Do not reply.
        >
        >To unsubscribe: send a blank email to nataphcv-request@... with a subject of unsubscribe.
        >
        >
        >For more information, see http://seven.pairlist.net/mailman/listinfo/nataphcv
        >
        >_______________________________________________
        >
        >
        >[Non-text portions of this message have been removed]
        >
        >
        >
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