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Am J Neurodegener Dis 2013;2(3):176-186

Review Article
Therapies for human prion diseases

Peter K Panegyres, Elizabeth Armari

Neurodegenerative Disorders Research Pty Ltd, 185 York St, Subiaco WA, Australia

Received August 5, 2013; Accepted August 30, 2013; Epub September 18, 2013; Published September 30, 2013

Abstract: The pathological foundation of human prion diseases is a result of the conversion of the physiological form
of prion protein (PrPc) to the pathological protease resistance form PrPres. Most patients with prion disease have
unknown reasons for this conversion and the subsequent development of a devastating neurodegenerative disorder.
The conversion of PrPc to PrPres, with resultant propagation and accumulation results in neuronal death and
amyloidogenesis. However, with increasing understanding of neurodegenerative processes it appears that protein-
misfolding and subsequent propagation of these rouge proteins, is a generic phenomenon shared with diseases
caused by tau, α-synucleins and β-amyloid proteins. Consequently, effective anti-prion agents may have wider
implications. A number of therapeutic approaches include polyanionic, polycyclic drugs such as pentosan polysulfate
(PPS), which prevent the conversion of PrPc to PrPres and might also sequester and down-regulate PrPres.
Polyanionic compounds might also help to clear PrPres. Treatments aimed at the laminin receptor, which is an
important accessory molecule in the conversion of PrPc to PrPres – neuroprotection, immunotherapy, siRNA and
antisense approaches have provided some experimental promise. (AJND1308003).

Keywords: Prion diseases, Creutzfeldt-Jakob disease, treatments, neurodegenerative diseases, protein misfolding,
protein propagation

Address correspondence to: Dr. Peter K Panegyres, Neurodegenerative Disorders Research Pty Ltd, 185 York Street,
Subiaco WA 6009, Australia. Tel: +61 8 6380 2255; +61 8 6380 2055; E-mail: research@ndr.org.au