A paper in today’s issue of Science describes a technique that could lead to the development of a simple blood test for prion diseases.
According to the prion hypothesis, a misfolded version of the prion protein, called PrPSc, is the infectious agent responsible for the transmission of spongiform encephalopathies, a group of neurodegenerative diseases including bovine spongiform encephalopathy (BSE, or ‘Mad Cow Disease’), scrapie and variant Creutzfeldt Jakob Disease (vCJD).
Claudio Soto and his colleagues, at the University of Texas Medical Branch, Galveston have invented a technique which they have used to detect the misfolded prion protein (PrPSc) in hamsters. The technique, called protein misfolding cyclic amplification (PMCA), is analogous to DNA amplification by polymerase chain reaction (PCR). Blood samples are first incubated; any PrPSc present causes normal prion proteins in the samples to adopt the malformed configuration and aggregate in chains. The samples are then treated with ultrasound, causing the breakdown of the chains into shorter chains which then go on to convert more of the normal prion proteins into the misfolded version.
Soto and his team used PMCA to detect the presence of the PrPSc protein in the blood of hamsters during the ‘silent phase’ of infection, just weeks after they had been infected with scrapie and long before the appearance of any neuropathology or symptoms.
The results of a recent study suggested that the incubation period of human prion diseases may be 50 years or more, and that there may yet be an epidemic of vCJD. The availability of a blood test based on the PMCA method could help to provide early diagnoses of human prion diseases and perhaps determine the extent of prion disease infection. One way in which people have been infected with vCJD is by receiving transfusions of contaminated blood. Another extremely useful application of the method would therefore be the analysis of blood which is to be used for transfusions.
“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,” says Soto. “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.”
“We’re now working with natural samples, both from humans and cattle but mostly from humans,” continues Soto, who has formed a start-up company, Amprion, which he hopes will soon provide the blood tests commercially.