MONDAY, March 18, 2002 (HealthDayNews) -- The type of brain protein linked to a family of fatal illnesses that include mad cow disease has also been found in mouse muscle tissue. And that may mean a medical breakthrough, of sorts.
The first-ever discovery of substances called prions in the skeletal muscle of mice could potentially pave the way for new methods of testing for mad cow disease or its deadly human equivalent, Creutzfeld-Jakob disease (CJD).
The usual ways to diagnose prion disease is to perform brain biopsies, which means euthanizing animals and dissecting their brain tissue or waiting until a human patient dies to perform a brain autopsy.
The family of prion diseases, including scrapies in sheep and goats, mad cow disease -- bovine spongiform encephalopathy (BSE) -- in cattle and Creutzfeld-Jakob disease in humans, are part of a group known as transmissible spongiform encephalopathies (TSEs).
In these diseases, abnormally shaped proteins cause prions to multiply and alter the shape of other proteins.
In the brain, the effect of these changes is dramatic. Holes form in brain tissue, until it takes the appearance of a sponge. With this damage comes difficulty with coordination, changes in behavior, and ultimately, death. There is no known cure for any prion disease.
Knowing that prions could be located in the brain, a team working with Nobel laureate Dr. Stanley Prusiner, who first identified prions in 1982, wondered whether prions could be located in the muscles of mice. And if that were possible, they wondered if prion levels would rise if the proteins were injected into the rodents' muscle.
Co-investigator Giuseppe Legname and his colleagues started by searching for prions in mouse muscle and isolating them, then injecting those prions into the muscles of other mice. This revealed that the prions were indeed infectious.
The next step was to breed mice in which the protein that sustains prion replication was produced only in muscles.
"Again, we found that prions were able to replicate in the muscles of these transgenic mice, indicating that possibly, replication of prions can occur in muscle without the need for having prions in the brain or lymphatic tissue," says Legname, an assistant adjunct professor at the University of California, San Francisco's Institute for Neurodegenerative Diseases.
The second significant finding of the study, which appears in tomorrow's issue of the Proceeding of the National Academy of Sciences, was that the highest levels of prions accumulated in the mice's hind legs.
"Our explanation is that, probably, there are other factors that are involved in prion replication," says Legname. "These factors are not yet discovered, but this suggests that in that particular region, there are higher concentrations of these co-factors, which sustains replication."
Shu Chen, an assistant professor of neuropathology at Case Western Reserve University's Institute of Pathology in Cleveland, says that this would be the first study suggesting that so-called "peripheral" prion proteins can be infectious.
But Chen is cautious about implications for testing for prions outside the brain, adding that prions may be detectable in muscle only in transgenic animals.
"In natural situations, you may not have the high expression in the peripheral tissue," he says.
Still, he says, the potential that a muscle biopsy could someday diagnose CJD in humans is desirable.
"If you're using the brain tissue, usually that's already too late," he says, meaning that a patient will already have developed symptoms or will be in the terminal stage of the prion disease.
Chen says the biopsies of peripheral systems may have potential both for less-invasive diagnostic examinations or for determining whether anti-prion therapies are having an effect.
Based on this study, Legname says, researchers should start screening the muscles of livestock for prions. He says that these studies must involve large numbers of animals, and look for the ideal biopsy site, which may vary by species.
"Now we might have the great possibility of doing these [biopsies] in a less-invasive way, while the animal or the patients are still alive," says Legname.
"Detection for clinicians right now is still very difficult," he says. "If we can actually provide a new tool for diagnosis, then the patient can take appropriate drugs as soon as possible."
He points out that working with larger animals will pose some technical problems, because the incubation period for prion diseases is much longer in large animals and humans.
What To Do:
To find out about prions, read Prusiner's article in Scientific American on the prion diseases.
For information on Creutzfeld-Jakob disease, visit the Centers for Disease Control and Prevention Web site, while for information on mad cow disease (bovine spongiform encephalopathy), try the Unites States Department of Agriculture.
