The
transmissible spongiform encephalopathies are rapidly progressive and invariably fatal
neurodegenerative diseases for which there are no proven efficacious treatments. Many approaches have been undertaken to find ways to prevent, halt, or reverse these
prion diseases, with limited success to date. However, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. There is increasing pressure to find effective decontaminants for blood supplies, as
variant Creutzfeldt Jakob Disease (vCJD) has been shown to be transmissible by blood, and to find non-toxic preventative
therapies, with ongoing cases of
Bovine Spongiform Encephalopathy (BSE) and the spread of
Chronic Wasting Disease (CWD). Within the realm of chemotherapeutic approaches, much research has focussed on blocking the conversion of the normal form of
prion protein (PrP(c)) to its abnormal counterpart (
PrP(res)). Structurally, these chemotherapeutic agents are often polyanionic or polycyclic and may directly bind PrP(c) or
PrP(res), or act by redistributing, sequestering, or down-regulating PrP(c), thus preventing its conversion. There are also some polycationic compounds which proport to enhance the clearance of
PrP(res). Other targets include accessory molecules such as the
laminin receptor precursor which influences conversion, or cell signalling molecules which may be required for pathogenesis. Of recent interest are the possible
neuroprotective effects of some drugs. Importantly, there is evidence that combining compounds may provide synergistic responses. This review provides an update on current testing methods, therapeutic targets, and promising candidates for chemical-based
therapy.