Researchers at the University of Alberta’s Centre for Prions and Protein Folding Diseases report finding a protective mechanism in cells related to the slow onset of symptoms, which could lead to methods for preventing the onset of neurological diseases such as Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) in cattle.

Their report, titled “Prion disease tempo determined by host-dependent substrate reduction,” is published in The Journal of Clinical Investigation.

The findings "present a breakthrough in understanding the secret life of prion molecules in the brain and may offer a new way to treat prion diseases," says David Westaway, PhD, a researcher on the project.  Quoted in an article in the Edmonton Sun, Westaway says "We think we have stumbled upon something unexpected, that the cells have a protective mechanism. And we are quite confident that finding is very solid, very robust, because we looked at six different types of prion disease and they all had the same effect."

Prion diseases such as CJD typically have long incubation periods, but can progress rapidly after the onset of symptoms, and there is no cure.

Using rodent models, the researchers found reductions in PrPC, the cellular precursor for the misfolded prion protein, during the incubation period. These reductions occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. They report this “downregulation” of PrPC is not discernible in animals with unusually short incubation periods but is evident in slowly evolving prion infections. “Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains,” the researchers note in the report’s abstract.

The group plans to continue research into ways to augment the protective response to keep prion diseases from advancing beyond their pre-clinical phase.