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Strongest proof yet found for prion hypothesis

UTMB scientists offer strongest evidence yet that infectious misformed proteins cause mad cow disease and other mysterious brain disorders

Researchers at the University of Texas Medical Branch at Galveston (UTMB) have produced the strongest proof yet that the mysterious and devastating brain diseases known as "transmissible spongiform encephalopathies" (TSEs) are transmitted by an infectious agent composed only of a malformed protein, and not a virus. TSEs, which can afflict both human beings and animals, include mad cow disease, new-variant Creutzfeldt-Jakob Syndrome, scrapie, kuru and chronic wasting disease.

This controversial "prion hypothesis" was proposed by Stanley Prusiner in 1982, and led to Prusiner receiving the Nobel Prize in Medicine in 1997. Until now, however, scientists have been unable to confirm its validity by causing a TSE in normal lab animals by infecting them with malformed proteins (dubbed "prions" by Prusiner) created entirely in a test tube. Such an approach eliminates the possibility that some other agent might be causing the disease.

In a paper scheduled to appear in the journal Cell on April 21, the UTMB researchers describe the use of a method they developed called "protein misfolding cyclic amplification" (PMCA) to vastly accelerate the activity of a small number of prions taken from infected hamsters and placed in test tubes containing healthy brain proteins. When the healthy proteins had been largely transformed into prions, the samples were diluted over and over again and the process repeated, until the only remaining prions were those that had been generated in the test tubes. These were then injected into the brains of healthy hamsters, which began showing TSE symptoms within four months and, on average, died less than six months after inoculation.

"For many years, people have tried to make these infectious prions in test tubes, because what is needed to prove the prion hypothesis completely is to be
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Source:University of Texas Medical Branch


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