Anti-prion drug mPPIg5 inhibits PrPC conversion to PrPSc

Prion diseases, also known
as transmissible spongiform encephalopathies, are a group of fatal
neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy
(BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein
only hypothesis' advocates that PrPSc, an abnormal isoform of the
cellular protein PrPC, is the main and possibly sole component of
prion infectious agents. Currently, no effective therapy exists for these
diseases at the symptomatic phase for either humans or animals, though a number
of compounds have demonstrated the ability to eliminate PrPSc in cell culture
models. Of particular interest are synthetic polymers known as dendrimers which
possess the unique ability to eliminate PrPSc in both an
intracellular and in vitro setting. The efficacy and mode of action of
the novel anti-prion dendrimer mPPIg5 was investigated through the creation of
a number of innovative bio-assays based upon the scrapie cell assay. These
assays were used to demonstrate that mPPIg5 is a highly effective anti-prion
drug which acts, at least in part, through the inhibition of PrPC to
PrPSc conversion. Understanding how a drug works is a vital component
in maximising its performance. By establishing the efficacy and method of
action of mPPIg5, this study will help determine which drugs are most likely to
enhance this effect and also aid the design of dendrimers with anti-prion
capabilities for the future.