GALVESTON, Texas -- Researchers at the University of Texas MedicalBranch at Galveston (UTMB) have found a way to detect in blood themalformed proteins that cause "mad cow disease," the first time such"prions" have been detected biochemically in blood.
The discovery, reported in an article scheduled to appear online inNature Medicine Aug. 28, is expected to lead to a much more effectivedetection method for the infectious proteins responsible forbrain-destroying disorders, such as bovine spongiform encephalopathy(BSE) in cattle and variant Creutzfeldt-Jakob disease (vCJD) in humans.The blood test would make it much easier to keep BSE-infected beef outof the human food supply, ensure that blood transfusions and organtransplants do not transmit vCJD, and give researchers their firstchance to figure out how many people may be incubating the disease.
"The concentration of infectious prion protein in blood is fartoo small to be detected by the methods used to detect it in the brain,but we know it's still enough to spread the disease," said UTMBneurology professor Claudio Soto, senior author of the Nature Medicinepaper. "The key to our success was developing a technique that wouldamplify the quantity of this protein more than 10 million-fold, raisingit to a detectable level."
Soto and the paper's other authors, UTMB assistant professorof neurology Joaquin Castilla and research assistant Paula Sa�, applieda method they call protein misfolding cyclic amplification (PMCA) toblood samples taken from 18 prion-infected hamsters that had developedclinical symptoms of prion disease. PMCA uses sound waves to vastlyaccelerate the process that prions use to convert normal proteins tomisshapen infectious forms.
Successive rounds of PMCA led to the discovery of prions inthe blood of 16 of the 18 infected hamsters. No prions were found inblood samples that were taken from 12 healthy control hamsters andsubjected to the same treatment.
"Since the original publication of a paper on our PMCAtechnology, we've spent four years optimizing and automating thisprocess to get to this point," Soto said. "The next step, which we'recurrently working on, will be detecting prions in the blood of animalsbefore they develop clinical symptoms and applying the technology tohuman blood samples."
Tests for infectious prions in cattle and human blood are badlyneeded. Because current tests require post-slaughter brain tissue foranalysis, in the United States only cattle already showing clinicalsymptoms of BSE (so-called "downer cows") are tested for the disorder.This is true even though vCJD potentially can be transmitted by animalsnot yet showing symptoms of the disease. (Only two cases of BSE havebeen found in American cows so far.) And although British BSE caseshave been in decline since 1992, scientists believe the British BSEepidemic of the 1980s could have exposed millions of people in the UKand Europe to infectious prions. The extent of the vCJD epidemic is yetunknown. So far the disease has killed around 180 people worldwide, butnumbers could reach thousands or even hundreds of thousands in thecoming decades. Prions have also been shown to be transmissible throughblood transfusions and organ transplants.
"Who knows what the real situation is in cattle in the UnitedStates? And with people, we could be sitting on a time bomb, becausethe incubation period of this disease in humans can be up to 40 years,"Soto said. "That's why a blood test is so important. We need to knowthe extent of the problem, we need to make sure that beef and the humanblood supply are safe, and we need early diagnosis so that whenscientists develop a therapy we can intervene before clinical symptomsappear--by then, it's too late."
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