TEST COULD IMPROVE DETECTION OF PRION DISEASE IN HUMANS

A highly sensitive post-mortem test could help scientists more accurately
determine if a person died of Creutzfeldt-Jakob disease (CJD), a human
neurological disorder caused by the same class of infectious proteins that
trigger mad cow disease, according to a new study supported in part by the
National Institutes of Health (NIH). The finding opens the possibility that
such testing might be refined in the future so it can be used to detect
prion disease in living people and animals before the onset of symptoms.

The test, called conformation-dependent immunoassay (CDI), was originally
developed to detect various forms of disease-causing proteins called prions
in cows, sheep, deer and other animals.

In the new study, researchers led by
Jiri Safar, M.D., Bruce Miller, M.D., Michael Geschwind, M.D., Stephen
DeArmond, M.D., and Nobel Laureate Stanley B. Prusiner, M.D., of the
University of California, San Francisco, found that CDI not only identifies
prions in human brain tissue but is faster and far more precise than the
standard immunological detection methods, which only detect a small fraction
of the infectious prions that may be in the brain.

The finding appears in the March 1, 2005 issue of the "Proceedings of the
National Academy of Sciences", <http://www.pnas.org>.

In the study, Prusiner and his colleagues extracted brain tissue from 28
people who had died of CJD. They tested these samples using CDI, which uses
highly specific antibodies that bind to all disease-causing prions in the
brain. They also used immunohistochemistry (IHC) to measure only the prion
proteins that are resistant to an enzyme called protease. Protease-resistant
prions are abnormal and usually infectious, meaning they can cause CJD and
other neurodegenerative diseases. CDI detected abnormal prions in all of the
sampled brain regions. In contrast, the researchers found that IHC detected
abnormal prions in less than 25 percent of the sampled brain regions. The
findings, according to the researchers, suggest that CDI could be used to
establish or rule out the diagnosis of CJD with greater accuracy than IHC,
particularly when a small number of samples are available. Prusiner and
colleagues are exploring the possibility of using CDI in living tissue, like
blood or muscle, to detect and diagnose prion diseases, such as CJD or
bovine spongiform encephalopathy (BSE, mad cow disease) while people or
animals are still alive.

"This research not only is an important advance for the detection and
diagnosis of prion diseases, but, with the identification of
protease-sensitive infectious prions, will lead to a better understanding of
the underlying disease processes," said Andrew Monjan, Ph.D., Chief of the
NIA's Neurobiology of Aging Branch.