Size matters in brain-wasting illness, state researchers say

By JENNIFER McKEE - IR State Bureau - 09/08/05

HELENA — Montana scientists have discovered that size matters when it comes to strangely misshapen brain proteins and the deadly ailments they cause like mad cow disease.

In a paper published today in the journal Nature, scientists at Rocky Mountain Laboratories in Hamilton show that big clumps of misshapen brain proteins called prions are not as effective at causing deadly brain disease as smaller ones. Really small pieces of the protein, however, don't seem to cause disease at all.

"This was totally surprising,'' said Jay Silveira, lead author of the paper who spent years working on the groundbreaking experiment.

Brain-wasting diseases like mad cow and chronic wasting disease in deer and elk are caused by a common bodily protein called a prion that inexplicably becomes misshapen and accumulates in the brain. There, the protein clumps into long strands, accompanied by pockets of dead brain tissue that give the brain a spongy appearance and always kills its host. The classic hole-filled look of stricken brains gave rise to the official name of the family such diseases: transmissible spongiform encephalopathies or TSEs. The diseases include mad cow, chronic wasting, scrapie in sheep, and a similar brain-waster in people caused by eating the meat of affected cattle.

Doctors diagnose TSEs by peering at slides of affected people and animals. Long, clumpy strands of misshapen prions are always visible, Silveira said, and many scientists long believed the bigger the clumps the more infectious they must be. The belief was so widespread, Silveira said, some researchers were pursuing treatments for TSEs and other brain diseases associated with protein clumps, like Alzheimer's, that would break up the deposits.

Silveira and Byron Caughey, who oversaw the research, assumed the experiment would end up confirming that conventional wisdom, too.

Instead they proved just the opposite and upended another long-held belief about prion diseases that even a single prion is enough to cause disease.

In fact, Silveira said, the experiment showed that below a certain size, the prions weren't stable and fell apart in the body, causing no disease at all. What's left is a sweet spot of maximum infection, he said, not too big, not too small.

A big clump of prions will still lead to deadly brain disease, Silveira said, it's just that pound for pound, the big prion dollops aren't as efficient at causing disease and death as the smaller ones. He thinks the bigger clumps may include a lot of wasted prions and only those at the end are able to cause disease.

The discovery is important because it changed the way scientists think about prion diseases and creates new ideas for possible treatments.

"This really changes the target that people may want to look at,'' he said.

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