Fall 2007
NIAID Discovery News
Breakthrough in Detecting Prion Infections
For more than a decade, researchers have faced a key challenge: how to rapidly and accurately detect even very small amounts of the infectious material—believed to be prions—that cause rare diseases of the brain known as transmissible spongiform encephalopathies (TSEs). Spongiform describes what prion diseases do to the brain—transform it into a sponge-like substance. Transmissible refers to the fact that these diseases are infectious. The early stages of prion diseases, which affect some animals, including humans, are usually asymptomatic. But by the time visible symptoms, such as staggered walking or slurred speech, appear, death is imminent.
Better Diagnostics Needed
Early detection is important for identifying prion contamination and for diagnosing TSE infections. Tests in rodents have shown that the earlier experimental treatments can begin in the disease process, the better they work. Until recently, the most sensitive prion detection method required weeks to detect sub-infectious amounts of prions, and it required a mixture containing normal brain tissue, not a practical approach for most purposes.
Now, scientists at NIAID’s Rocky Mountain Laboratories have developed a new prion detection method that produces ultrasensitive results in just 2 to 3 days and substitutes inexpensive synthetic reaction ingredients for brain tissue. This method also allowed the detection of TSE disease in animals using spinal fluid samples. Other even less invasive methods, such as using blood samples, are being investigated.
“This is something that laboratories around the world have been trying to accomplish for years,” says NIAID senior investigator Byron Caughey, Ph.D. “We think this work will lead to an inexpensive, rapid tool for detecting prion infections in mammals, medical instruments, blood transfusions, and food items.”
Prions Trigger Chain Reaction
Ryuichiro Atarashi, M.D., in Dr. Caughey’s group made the breakthrough by developing a method by which prions are induced to initiate a chain reaction that converts an artificial protein to a warped form. The warped form of the protein is then easily detected as an indicator of the presence of prions.
The new detection method is extremely sensitive. One lethal dose of a TSE agent is defined as the amount needed to make 50 percent of injected mammals sick. Dr. Caughey’s group detected infectious prion protein equal to a tiny percentage, about 3/1000, of a lethal dose.
Dr. Caughey cautions that so far his research group has proven the utility of the method only in rodents and using scrapie, a type of TSE that affects sheep. But his group already is working to adapt the method to other TSEs, such as mad cow disease, a type of prion disease of cattle. Mad cow disease, or bovine spongiform encephalopathy, is probably the best known prion disease because it can infect humans. Other prion diseases include Creutzfeldt-Jakob and kuru, which also afflict humans; and chronic wasting disease, which affects deer and elk in North America.
Dr. Caughey says he is confident that the new test also will provide new opportunities for scientists to better study the structure of prion proteins.
View a video explaining NIAID scientist Byron Caughey's research on developing a better test for the proteins responsible for mad cow disease (Windows Media Player Format, SMIL captioned, 3 MB, Credit: ScienCentral, Inc.)
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—Ken Pekoc
Reference
Atarashi, R. et al. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nature Methods DOI: 10.1038/nmeth1066 (2007).
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