- Antibodies which "cured" mouse cells of scrapie
have raised hopes that the human form of mad-cow disease will one day be
treatable.
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- So far, 100 people have succumbed to variant Creutzfeldt
Jakob Disease (vCJD). Thousands more could fall sick, warn epidemiologists,
so a treatment is needed urgently.
-
-
- But pioneers of the latest breakthrough warn against
false hope. "These are tissue culture cells, so we still have to find
whether the same thing happens in animals, let alone in people," says
Charles Weissmann, who led the research at the Medical Research Council's
Prion Unit at St Mary's Hospital, London.
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- Weissmann grew mice cells in the lab and infected them
with a strain of mouse scrapie to mimic infection with vCJD. As expected,
the cells began producing prions, malformed versions of a normal protein
found on the cell surface, especially in brain cells.
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- It is these prions, given the symbol PrPSc, which clog
up the brains of people with vCJD, sheep with scrapie and cows with BSE.
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- But when Weissmann exposed the infected cells to an antibody
codenamed 6H4, it halted the production of the prion proteins. The cells
remained "healthy" for at least six weeks after the antibody
treatment had been given.
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- Destroying the indestructible
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-
-
- As an unexpected bonus, prion protein that had accumulated
beforehand disappeared as well. This was a surprise, as prion proteins
are widely thought to be virtually indestructible.
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- "It means that, contrary to what people thought,
PrPSc is not that stable," says Weissmann. "As it turns out,
it is destructible ... and it's probably enzymes that degrade it."
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- The antibody works by blocking the normal version of
the prion protein, called PrPC and produced on the surface of cells. He
thinks this lends weight to the theory that it is through physical contact
with this normal version of the protein that the abnormal prion protein
infects a cell and replicates itself inside.
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- To add further credence to this, Weissmann treated some
of the infected cells with a bacterial enzyme that strips a cell of all
its surface proteins, including PrPC. As with the antibody, production
of the prions dried up once PrPC was no longer available.
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- Alzheimer's "vaccine"
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-
-
- Encouraging as the results are, Weissmann warns that
the treatment might not work in people. "The next step is to try it
in mice," he says.
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- Even if it worked in animals, researchers would need
to develop different antibodies that mask the human PrPC protein. Secondly,
researchers would need to find a way of getting the antibodies into the
brain, again, not a trivial task.
-
-
- But he says that similar approaches to treat Alzheimer's
disease have begun to yield interesting results. Elan Pharmaceuticals in
Dublin, Ireland, announced on Monday progress with AN-1792, a "vaccine"
against Alzheimer's disease.
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- The vaccine compound resembles amyloid protein, the substance
in the plaques that affect the brains of people with Alzheimer's. The hope
is that AN-1792 tricks the body's immune system into attacking and disposing
of the plaque.
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- Elan claims that tests on 100 patients with mild to moderate
Alzheimer's showed that some developed an "immunological response"
to AN-1792. Elan is now planning tests in 375 patients in the US and Europe.
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- Journal reference: Proceedings of the National Academy
of Sciences (vol 98, p 9295).
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- http://www.newscientist.com/news/news.jsp?id=ns99991065
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