Abstract

Prion diseases are rare, highly destructive neurodegenerative diseases with no known cure or treatment – representing an urgent unmet clinical need. The mechanism of prion diseases is rather unusual, with the infectious agent being a misfolded version of an endogenous protein. This infectious, misfolded protein is able to promote the misfolding of healthy prion protein, spreading the disease, which ultimately causes toxic aggregates to accumulate. We propose to use PROTAC technology to deplete the reservoir of PrP and starve the infectious agent as an exciting and novel therapeutic strategy.