Prion principle proved
Captured protein couple may help treat
brain disease.
4 April 2003
HELEN PEARSON
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| Infected beef is thought to
cause vCJD. |
| © GettyImages |
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Researchers in Switzerland claim to have proved a long-standing
theory about prions: that the proteins couple up to breed mad cow
disease. Their experiments should fuel the search for a cure.
In both the animal disorder and its human equivalent, variant
Creutzfeldt-Jakob disease (vCJD) warped prions clump in the brain,
eventually destroying it. Misshapen prions were thought to latch
onto and warp normal ones. But scientists had not captured this
liaison taking place in sick animals.
Now Adriano Aguzzi of University Hospital Zurich, Switzerland and
his colleagues have caught prions in the act1.
They genetically engineered mice to carry a new, artificial version
of prions with a tag. Unlike the real thing, this makes them easy to
isolate from cells.
They then infused the animals' brains with mangled prion proteins
responsible for the sheep analogue of BSE, scrapie. As predicted,
they found the artificial prions attached to the mutant form.
"It's the cleanest evidence yet" for the interaction, says prion
researcher Michael Scott of University of California in San
Francisco. "It mimics the normal situation."
The coupled proteins could help to screen drugs that might block
the prion-prion contact, or to identify other proteins that get
involved. "It could really help in working out how this process
occurs," Scott says.
Slow progress
125 British people have died from the brain destroying vCJD since
1995 - probably caught from eating beef. According to recent
predictions, the future vCJD death toll for Britain alone could lie
between 10 and 7,000. There is no known cure.
The artificial prions might be the basis of a new therapy,
Aguzzi's team says, because although they bind mutant prions, they
resist being transformed themselves. Mice with the modified prion
survived for at least three months longer than those without.
Aguzzi's team engineered the artificial prions by fusing a normal
prion protein with part of a human antibody. This made the protein
soluble and easy to extract from a mash of cells - along with other
proteins attached to it.
Prion researchers are already attempting to use drugs and
antibodies to stop misshaped prions proliferating and hence delay
vCJD. "We don't know at present if artificial prions will be better
than antibodies," says Neil Cashman who studies brain disease at the
University of Toronto, Canada. |
