Researchers have developed a way to vaccinate mice against deadly prion diseases, which include scrapie, kuru, mad cow disease, and Creutzfeldt-Jakob disease. The findings, presented today at the annual American Academy of Neurology meeting in Boston, suggest that these degenerative brain diseases can be stopped if caught early enough.
Prion proteins, expressed in neurons, are found in one form in healthy individuals. But when even one protein becomes misfolded--or a misfolded protein enters the body through food, such as infected beef--it changes the conformation of all the prions around it (ScienceNOW, 21 April 2005). The misfolded proteins clump and destroy neurons, creating tiny holes in the brain. Prion diseases have no known cure. Previous attempts at vaccines have delayed the onset of prion diseases, but never prevented them.
Searching for a more effective vaccine, a team led by neuropathologist Thomas Wisniewski of the New York University School of Medicine in New York City took a new approach. They genetically modified a strain of Salmonella bacteria to express prion proteins. When researchers fed these bacteria to mice, the bugs multiplied in the rodents' guts, and the animals developed antibodies against the prions. A month later, the researchers fed the mice disease-causing prions; mice that had developed antibodies against the prion proteins stayed healthy for the remainder of the study, 400 days, while those not inoculated with the modified Salmonella developed a degenerative brain disease, like mad cow disease, and died within 200 days. Further work explained the difference: Prion antibodies in the gut stopped the misfolded proteins from spreading into the bloodstream.
The ultimate payoff may not be a vaccine protecting humans against Creutzfeldt-Jakob and other prion diseases, Wisniewski says. Instead, it makes more sense to target high-risk animal populations. "You could formulate this type of vaccine for the deer and elk population of the Western United States," he says, "and that would prevent the potential to spread to human populations through hunters."
Vaccination is one of the best strategies for combating prion diseases, says neuroscientist Neil Cashman of the University of British Columbia in Vancouver, Canada, because misfolded prion proteins are large and somewhat unstructured, making them difficult drug targets. "Antibodies, at least from a theoretical point of view, will have more utility in misfolding diseases than small molecules."
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