Prion prevention

Resistance and rapid testing are among potential new tools to combat prion disease.

Sep 27, 2002
Emma Hitt(

Transgenic mice resistant to Bovine spongiform encephalopathy (BSE) could pave the way to the breeding of resistant cattle, researchers reported this week in the Proceedings of the National Academy of Sciences (PNAS). Jiri Safar at the University of California, San Francisco (UCSF) and colleagues found that gene alterations caused mice to express a mutant form of BSE prion, which made the animals resistant when injected with high doses of the disease-causing form of prion.

BSE, also known as 'mad cow' disease, can cause variant Creutzfeldt-Jakob disease (vCJD), a rare but ultimately fatal brain disease, in humans who eat infected beef. The disease-causing agent, which is transmitted from sheep to cattle to humans, arises from a prion protein normally found on the surface of brain cells, but which has become modified and is less soluble and more resistant to enzyme degradation than the normal form.

Transgenic mice expressing resistant forms of prion protein at levels equal to wild-type mice remained healthy for more than 550 days, according to Safar. The mutations were polymorphic variants of prion protein, Q167R and E219K, and were the same as those that had previously allowed some sheep and humans to naturally resist infection.

In prion diseases, a misfolded isoform of the normal prion protein stimulates the production of yet more misfolded forms by causing even the normal form to misfold. But the variant forms introduced in the mice act as a dominant negative protein and inhibit this conversion.

Whether this research will eventually translate into the breeding of resistant livestock is unclear, but Safar told The Scientist that the findings "raise the possibility of producing prion-resistant livestock that express prion protein with a single amino acid substitution." He added that "because sheep homozygous for such a mutation already exist, breeding populations of resistant sheep is a reasonable undertaking."

The next step for Safar's team, which includes Nobel laureate Stanley Prusiner, who discovered the role of prion proteins in disease, is to inoculate transgenic mice expressing mutated sheep prion protein with many different strains of prions to see if resistance is far-reaching.

Until resistant animals can be bred however, stepped-up efforts are being made to prevent the spongiform encephalopathies from entering the human food chain in the first place. In August of this year, the U.S. Department of Defense (DOD) announced a $42 million National Prion Research Program, adding to the approximately $20 million already devoted annually by the National Institutes of Health (NIH) to prion research. A primary goal of the DOD program is development of a rapid detection test to diagnose the presence of prion diseases in living animals and people.

According to Jim Rodgers with the USDA's Animal and Plant Health Inspection Service, various companies have already begun the application process for rapid kits to diagnose scrapie and chronic wasting disease (CWD), which infects deer and elk. "A simple new test that can be conducted on the spot at slaughterhouses will be able to detect BSE, CWD, vCJD, and scrapie," said Robert Petersen with Prion Developmental Laboratories, a manufacturer of one of the tests under review. "I would anticipate that we could have USDA approval for the CWD and scrapie tests within 6 months," he said.