Management and prevention of human prion diseases

Abstract

Prion diseases are a group of fatal neurologic disorders that affect humans and animals and for which there is no available therapy. The basic pathogenic mechanism is linked to posttranslational changes of the host cellular prion protein (PrP(c)) into a pathologic conformer (PrP(TSE)) that has a strong tendency to aggregate and form amyloid fibrils. In humans, the most common form of the disease is sporadic Creutzfeldt-Jakob disease (CJD), which equally affects females and males of all ages and all ethnic groups. Sporadic CJD has an overall mortality rate of approximately one to two cases per million people per year, with peak incidence in individuals 60 to 70 years old. Approximately 10% to 20% of CJD cases appear within families and are linked to point or insert mutations in the prion protein gene (PRNP). Both sporadic and genetic prion disorders are transmissible to a wide range of laboratory animals by the injection of crude brain homogenates.