December 13, 2010

Early Prion Detection May Be Possible

Electron microscope image showing clumps of prion fibers This image, magnified 100,000 times using a transmission electron microscope, shows thread-like structures of prion protein.NIAID/RML.

Researchers have developed a method for detecting prions that may lead to a practical test for diagnosing the fatal brain conditions caused by these infectious agents.

Prion diseases, also known as transmissible spongiform encephalopathies, include mad cow disease in cattle, scrapie in sheep and Creutzfeldt-Jakob disease in humans. These diseases are characterized by sponge-like holes in brain tissue. They are notoriously difficult to diagnose, untreatable and ultimately fatal.

Prions are actually misfolded forms of proteins naturally found in the body. Prions can convert normally folded prion protein molecules into an infectious form when they come in contact with each other. These misshapen prion proteins clump together and accumulate in brain tissue.

Miniscule amounts of infectious prions found outside the brain can be detected by current diagnostic tests, but these methods lack the speed and convenience needed for routine use. Other quicker approaches aren't sensitive enough to detect low levels of infection. A research team led by Dr. Byron Caughey of NIH's National Institute of Allergy and Infectious Diseases (NIAID) has been working to develop a better method for quickly detecting small amounts of prions.

The researchers described their new method—called real-time quaking-induced conversion, or RT-QuIC—in the December 2, 2010, online edition of PLoS Pathogens. RT-QuIC is about 50-200 times faster and much less expensive than animal bioassays that detect similarly small amounts of disease-causing prions.

RT-QuIC takes advantage of the ability of tiny amounts of prions to seed the misfolding of normal prion proteins in a test tube. The method involves testing a range of dilutions to see at what point the sample loses its seeding activity.

The scientists tested tissue samples from infected deer and sheep and were able to distinguish infected animals from normal ones in 2 days or less. They were also able to detect prions in nasal washes from infected hamsters.

"Although relatively rare in humans and other animals, prion diseases are devastating to those infected and can have huge economic impacts," says NIAID Director Dr. Anthony S. Fauci. "Scientists have promising concepts for developing therapies for people infected with prion diseases, but treatments are helpful only if it is known who needs them. This detection model could eventually bridge that gap."

Along with optimizing their test in the laboratory, the researchers are teaming up with other laboratories to extend the applications of RT-QuIC. Similar approaches might also aid the diagnoses of additional neurodegenerative diseases, such as Alzheimer's, Huntington’s and Parkinson's.

Related Links