New test may spot mad cow-type disease in blood

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Scientists at the University of Texas Medical Branch in Galveston are developing a highly sensitive blood test for detecting prion particles, the infectious agents responsible for scrapie in sheep, mad cow disease, and the human form of the disease called variant Creutzfeldt-Jakob disease.

Prions are misfolded rogue proteins that can replicate and build up in the brain. Up until now, prions could only be detected biochemically in the brain and some lymph tissue, Dr. Claudio Soto and his associates explain in the online issue of Nature Medicine.

Levels in blood are generally too minute to be detected with biochemical methods. However, if prions could be identified in the blood, it might be possible to treat the condition at an early stage, before permanent brain damage occurs, the investigators suggest.

“The problem with current tests is they have low sensitivity,” Soto told. “They can detect animals that are symptomatic or about to get disease, but the time from when the animal is first infected to the time they develop clinical symptoms can last several years.”

The team’s new technique, called “protein misfolding cyclic amplification” (PMCA) expands the amount of prions by exposing them to sound wave energy, or sonication. “We mimic the molecular process by which abnormal protein transforms normal protein in the brain and we speed it up,” Soto said.

“We calculate that for each abnormal protein we have in a sample we can produce at least 10 million molecules in a matter of a few days,” an amount that is then detectable by standard assay methods.

So far the technique has been tested with animals, but ultimately Soto hopes his group can develop the means to screen human blood in populations at high risk for variant Creutzfeldt-Jakob disease, because of their exposure to meat from animals with mad cow disease.

“We know that from the time people get infected to the time they develop clinical symptoms can last up to 40 years, so we still have 20 years to go before we see full extent of the disease,” he said, referring to the situation that arose in the 1980s.

Soto believes that once the infection can be recognized, companies will direct their resources toward developing therapy before irreversible brain damage occurs.

SOURCE: Nature Medicine, online August 28, 2005.

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