Recent developments in therapeutics for prion diseases

Abstract

Background: Conformational conversion of the normal prion protein PrP^c into its pathogenic form, PrP^Sc, is the central event in the pathogenesis of prion diseases, including Creutzfeldt–Jakob disease in humans and bovine spongiform encephalopathy in cattle. This constitutive conversion results in accumulation of PrP^Sc in the brain and many lines of evidence indicate that the accumulated PrP^Sc may be detrimental, causing degenerative neuronal cell death. Objective: Therapeutic compounds for prion diseases must reduce PrP^Sc in affected brains. Many compounds have been identified to reduce PrP^Sc levels in infected cells and some were partially effective in infected animals, prolonging incubation or survival times. Clinical trials have only recently started with a few of these compounds. They are systematically introduced and their performances and possible mechanisms summarised. Methods: Bibliographic research was carried out using the PubMed database. Patent literature was searched using the UK Intellectual Property Office website. Results/conclusion: No compounds reported so far have proven to be therapeutically effective against prion diseases, due to inadequate access to brains through the blood–brain barrier. Moreover, due to lack of diagnostic indicators for presymptomatic individuals, the compounds must be given to clinically advanced patients, reducing their effectiveness. Thus, it is also important to resolve these problems to develop therapeutically effective compounds for prion diseases.

Keywords::

• prion
• prion disease
• prion protein
• therapeutics

Acknowledgement

The author thanks K Murashita for figure preparations.