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Prion find points way to test for human 'mad cow' disease

'Silent' vCJD phase can last 40 years in humans; assay could reveal extent of problem and stop further infection via transfusions and transplants

In the July 7, 2006, issue of the journal Science, researchers at the University of Texas Medical Branch at Galveston (UTMB) describe experiments that may soon lead to a test that will enable medical science to estimate how many people are infected with the human form of mad cow disease, which can take as long as 40 years before manifesting itself.

Such a blood test could also help prevent accidental transmission of the malformed proteins that cause variant Creutzfeldt-Jakob disease (vCJD) via blood transfusions and organ transplants, the scientists suggest.

Done in hamsters, the experiments are the first ever to biochemically detect the malformed proteins during the "silent phase" of the disease--just weeks after the animals were infected and months before they showed clinical symptoms.

The scientists say that they detected prions--the infectious proteins responsible for such brain-destroying disorders as bovine spongiform encephalopathy (BSE) in cattle and vCJD in humans--in the blood of the hamsters in as few as 20 days after the animals had been infected. That discovery occurred about three months before the hamsters began showing clinical symptoms of the disease, the Science paper reports.

To detect the very small quantities of prions found in blood samples, UTMB professor Claudio Soto, assistant professor Joaquin Castilla and research assistant Paula Saá used a technique known as protein misfolding cyclic amplification (PMCA), invented by Soto's group, which greatly accelerates the process by which prions convert normal proteins to misshapen infectious forms.

"With this method, for the first time we have detected prions in what we call the silent phase of infection, which in humans can last up to 40 years," said Soto, senior author of the Science paper.

"The concern is that if many people are incubating the disease silently, then secondary transmission from human to human by blood transfusion or surgical procedures could become a big problem," he continued. "This result is an important step toward a practical biochemical test that will determine how common variant CJD is, and keep contaminated blood and organs from spreading it further."

Creating such a test is a high priority for Soto, who is also director of UTMB's George and Cynthia Mitchell Center for Alzheimer's Disease. "We're now working with natural samples, both from humans and cattle but mostly from humans," he said. With an eye toward making a human test commercially available, Soto and UTMB recently formed a startup company, dubbed "Amprion."

"All our effort so far has been to prove the scientific concepts, so we're building this company to go into issues of development, scalability and practicality," Soto said. "We are hopeful that development of this technology into a useful blood test will be a pretty straightforward process."

Jim Kelly | EurekAlert!
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