Scripps Florida researchers develop new test for mad cow prions
FL – Current tests to identify specific strains of infectious prions, which
cause a range of transmissible diseases (such as mad cow) in animals and
humans, can take anywhere from six months to a year to yield results – a
time-lag that may put human populations at risk.
Now, a group of scientists from The Scripps Research Institute's Florida
campus have developed a new method that cuts this critical time lag by
The new research was published in the open-access journal PLoS ONE on May 29,
"Because some prion strains are pathogenic for humans and some are not,
it's vital that we know the difference when we find them in the field and
when we study them in the laboratory," said Corinne Lasmézas, a
professor in the Department of Infectology at Scripps Florida who led the
"Currently, the identification process for mouse-adapted strains takes
between six and eight months and can take as long as a year, depending on the
strain. Our accelerated method reduces that time to around four months."
The new method for distinguishing among various strains combines a transgenic
mouse model with a rapid and sensitive cell-based procedure, the Cell Panel
Assay developed by Scripps Florida's Charles Weissmann (chair of the
Department of Infectology) and Sukhvir Mahal (senior staff scientist), also
investigators on the new study.
"There are about 20 prion strains known in mouse models," Lasmézas
said. "We still don't understand what determines the difference among
strains even though it's very important, especially for any potential
therapeutic development. Our new method should help quicken the pace of
The Mysteries of Prions
Prion diseases, also called spongiform encephalopathies, are a group of
closely related, fatal neurodegenerative disorders that affect mammals,
including cows, sheep, and deer, as well as humans.
Different strains of the infectious agent, called a prion, cause mad cow
disease, chronic wasting disease, and different forms of scrapie and human
Mad cow disease has had devastating consequences for bovine livestock
populations, particularly in Europe, and for humans who have consumed
contaminated beef products.
To date, there have been more than 200 recorded human fatalities worldwide
due to mad cow disease. Creutzfeldt-Jacob disease, a low-incidence but always
fatal disease, affects humans in all countries.
Prions consist mainly or entirely of an abnormal form of a normal cellular
protein. They multiply by converting their normal counterparts into a
likeness of themselves, which may aggregate to form deposits called amyloid.
Accumulation of different kinds of amyloid plays a role in a wide range of
neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.
Currently, different varieties of prion strains are identified in mouse
models according to incubation time, clinical symptoms, and localization of
In the new test developed by Lasmézas and Weissmann, a transgenic mouse line
called Tga20 plays an important role, because it succumbs rapidly to prion
"The prions primarily target the brainstem and the thalamus of this
transgenic mouse, explaining why these animals have a shorter incubation time
than their normal counterparts," Lasmézas said.
"The prion aggregates also don't spread evenly to other brain regions,
and their distribution is characteristic for different strains."
Importantly, the brain tissue can be subjected to the Cell Panel Assay, which
unlike the current histological method, doesn't require time intensive
examination of brain lesions and can be completed within two weeks, Lasmézas
added. The test has been partially automated.
Development of the method provided the scientists with the opportunity to
make the observation that there was, in some brain regions, little
relationship between the amount of abnormal prion protein deposition and the
amount of normal prion protein. This was something of a surprise, Lasmézas
said, but not totally unexpected.
"We and others believe that the prion protein may not be the sole player
in these diseases," she said.
"Perhaps there is a co-factor, or perhaps the protein structure differs
somewhat from one brain region to the next. We don't know. Just like we don't
really know the reason for the different behavior of the various prion
strains—is this cause or effect? Our new method should help accelerate the
process of discovery."