prions. cheese. mad cow disease. milk.

Don Saklad dsaklad at
Thu Jan 8 10:18:35 EST 2004

Here's an article by Robert Cooke

By Robert Cooke Your Life your connection to The Boston Globe 

   Home > Your Life > Health & Fitness > Diseases & Treatments
   The Boston Globe 

We all have prions, the cause of mad cow, but why?

   By Robert Cooke, Globe Correspondent, 1/6/2004

   The early-morning news from Stockholm in October 1997 was a shocker:
   Neurobiologist Stanley Prusiner had received the Nobel Prize in
   medicine for his pioneering work on prions, the mysterious misshapen
   proteins that cause mad cow disease. The prize was immediately
   controversial because many researchers still thought the idea was

   After all, as infectious disease agents, prions break all the rules.
   They seem to have no genetic material of their own. They are not
   subject to immune attack. And they can't be "denatured" by heating,
   digesting them with enzymes or hitting them with chemicals. Many of
   the important answers were still missing.

   Almost seven years later, the first case of mad cow disease has been
   confirmed on US soil, and many important answers are still missing.
   Nonetheless, Prusiner's work -- and similar work by dozens of other
   research teams -- is looking better and better.

   "We do have some understanding of this agent" and how a simple
   protein can wreak such havoc in the brain, said Susan Lindquist,
   director of the Whitehead Institute for Biomedical Research in
   Cambridge, who has spent years studying prions.

   It's now clear that a prion protein -- in its dangerous, abnormal
   form -- has a sort of "Midas touch" that ruins normal prion
   molecules that it contacts. When a bad prion meets its normal
   neighbor, normal becomes abnormal, and then goes on to convert other
   normals into bad guys.

   Also, it's just a change in shape, not a change in chemistry, that
   makes everything go haywire. The normal prion protein seems to twist
   into a new, more stable abnormal form that persists in damaging
   brain cells. As each abnormal prion kicks others into abnormal
   shape, it's rather like an atomic chain reaction, only slower. The
   disease progresses as bad prions accumulate, kill nerve cells and
   eventually leave the brain in tatters.

   Research has shown that the normal prion protein, in its
   nonpoisonous form, must be playing some important role in the body,
   especially in the nervous system. It is found in all tissues, but is
   particularly abundant in cells of the spinal cord and brain. This
   tells scientists the protein is there for an important reason.

   "It is a natural protein with a natural function, something specific
   for neural function," said neuroscientist Huntington Potter,
   formerly at Harvard, now interim director of the Alzheimer's Center
   and Research Institute in Tampa, Fla. "But it also has a natural
   tendency to flip into an alternate shape, and it forms long fibers
   that accumulate and kill brain cells."

   Additionally, scientists at the Whitehead Institute, an affiliate of
   MIT, and at Columbia University in New York City, have uncovered
   hints that the abnormal prion protein may not really be a villain.
   The new work, published last month in the journal, Cell, suggests
   that the "normal" folding of the protein might actually be a resting
   or dormant phase, while the supposedly toxic form is the active
   version, perhaps playing some role that helps with memory.

   Lindquist collaborated in this work with a team led by Nobel
   laureate Eric Kandel at Columbia. And their findings suggest that
   the poisoning effect may be derived from something else, perhaps a
   toxin of some sort that is produced in response to accumulating

   "We don't know what protein is the toxic species," Lindquist

   Lindquist also said there is some evidence that the victim's own
   immune system somehow helps infectious prion particles -- those that
   arrive in the gut from eating an infected animal -- get into a new
   host's tissues. First, she said, the entering prions somehow avoid
   being chewed up by acids and enzymes in the gut.

   Then "the immune system is what does us in," she said. Rather than
   attack the prion as a foreign invader, or just ignore it, "the
   immune system carries it in," apparently through small areas in the
   gut called Peyer's patches. How that occurs is also not known.

   Researchers hope that by focusing intensively on understanding the
   disease, they can find ways to stop it, or repair the damage. So
   far, nothing really works, although there are hints of potential
   drug treatments that may yet emerge.

   "It is a deadly disease, invariably fatal, and we don't know how to
   attack it therapeutically," said Giuseppe Legname, a member of
   Prusiner's team at the University of California at San Francisco.
   "But we have a [potential] treatment -- an antimalaria drug -- that
   is working in laboratory animals and is very promising."

   No tests have been done in patients there, however, in part because
   there are so few patients who can be studied.

   Other researchers, such as Lindquist, have been focusing in part on
   using truly modern weapons, called monoclonal antibodies, against
   prions. These molecules, made by the immune system, can now be
   tailored in the laboratory to recognize almost any protein and then
   stir the immune system to attack it. The problem has been that
   because a prion protein is inborn -- a part of the body rather than
   a foreign microbe -- the immune systems tends to view it as "self,"
   something to be ignored.

   "You can't imagine how hard we've worked to get antibodies that will
   recognize only the abnormal form" of the prion protein, she said. If
   that can be done, it may be possible to alert a patient's immune
   system to destroy only the bad prions, leaving the good proteins
   undamaged. Antibodies could also provide a basis for quick and
   accurate tests for diagnosing animals and people.

   Tests also might become available to spotting prion contamination of
   donated human blood. At present, according to the American Red
   Cross, the blood supply is being protected by abstinence; donors are
   asked not to give blood if they've lived six months or more in
   Europe, or three months in the United Kingdom, where mad cow disease
   hit hardest.

   The human prion diseases known so far are Creutzfeld-Jakob disease,
   Gerstmann-Straussler-Scheinker syndrome, Fatal Familial Insomnia,
   Kuru, and Alpers syndrome. To some degree they seem to be inherited
   -- a mutant gene may be involved -- yet Kuru and mad cow disease
   proved that prions can be infectious, transmitted via nervous system
   tissues included in foods.



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