Abstract:

Despite intensive research, most neurodegenerative diseases cannot be cured and for some of them no treatment is available to increase survival or quality of life. Among the latter are prion diseases, fatal and transmissible neurodegenerative diseases of humans and other animals. Examples are Creutzfeldt-Jakob disease (CJD) in man, bovine spongiform encephalopathy (BSE, also known as mad cow disease) in cattle, scrapie in sheep and goats, and chronic wasting disease (CWD) in cervids. Most human prion diseases manifest sporadically, but also genetic and infectious origins are known. Prions, the causal agent of prion diseases, are composed solely of protein, namely a misfolded isoform of the cellular prion protein PrPC, termed PrPSc. They are transmissible within and between species. Human-to-human transmission can occur through medical procedures (e.g.,neurosurgery) and results in iatrogenic CJD (iCJD). The largest number of iCJD cases worldwide has been reported upon treating growth hormone deficits with prion-contaminated cadaveric pituitary-derived human growth hormones. Transmission of BSE from cows to humans is to date the only example of zoonotic prion transmission resulting in variant CJD. Whether CWD is transmissible to humans is unknown but represents a current threat due to expansion of geographic distribution within and beyond North America and in light of a novel study indicating oral transmission to non-human primates. In this context, finding a treatment against prion disease is of primary importance.