91av

IT MIGHT one day be possible to slow the progress of prion diseases—by
adding yet more prions. Researchers at the University of California, Davis, say
their computer model supports the controversial theory that you could treat such
diseases with a dose of normal prions from another species.

“It is an elegant mathematical model, one that suggests a route to therapy,
and one that is supported by considerable biological evidence,” says Mike Scott,
a prion researcher at the University of California, San Francisco. “But there
are some major hurdles that must be overcome before we know whether this
approach will prove to be of use.”

Prion diseases are triggered by an abnormal form of the protein PrP, which is
found on the surface of brain cells. If a little abnormal PrP gets into the
brain, it makes more of itself by converting normal PrP into the abnormal form,
which clumps together to form damaging “plaques”.

Biophysicist Daniel Cox and his colleagues have now come up with a simplified
model of how these plaques grow that predicts how long it takes the disease to
develop. They say the model’s predictions closely match what is seen in lab
experiments.

Such experiments have also revealed a species barrier to prion transmission.
For example, abnormal mouse PrP is good at infecting hamsters, but hamster PrP
isn’t so good at infecting mice. So the team looked to see if adding normal
hamster PrP to the brain of a mouse already infected by abnormal mouse PrP would
affect incubation time.

According to the model, this would indeed slow the progress of the disease.
When the normal hamster PrP comes into contact with developing mouse PrP
plaques, it forms a coat of abnormal hamster PrP around them, the researchers
say.

However, this is only true if the hamster PrP is converted into the abnormal
form faster than mouse PrP. What’s more, you’d have to inject large
concentrations of normal hamster PrP. And that’s a major obstacle, says Scott.
“The problem that we and others have faced in trying to actually do such
experiments is that we have not yet found a way to deliver PrP.”

Peter Lansbury, a prion researcher at Harvard, says there are reasons to
believe such treatments would work. He points out that you can treat sickle cell
anaemia by triggering production of fetal haemoglobin, which stops the clumping
of the abnormal form of adult haemoglobin that causes the disease.

But the build-up of hamster prions in the mouse is worrying, Lansbury says.
“Their presence may increase the rate of conversion of mouse prions and will, in
my opinion, not delay onset.” However, there might be a mutant form of hamster
PrP that could bind to the abnormal mouse form but not turn into the abnormal
form itself, he says.

Others aren’t convinced. “It seems very unlikely that injecting normal
cellular prion protein will prevent the development of disease,” says Simon
Hawke, a neuroscientist at Imperial College, London.