Therapeutic interventions ameliorating prion disease

Abstract

Of the many unresolved issues in relation to prion diseases, effective treatments remain an elusive exigency, although some progress has been made. This review describes disease-ameliorating therapeutic strategies reported to date in animal models of prion disease, as well as providing a brief overview of selected completed human treatment trials. Included in vivo studies have been broadly dichotomized according to the time of introduction of the treatment in relation to animal inoculation and also according to their possible principal mechanism of action, although the latter is not always entirely clear, and often there is likely to be more than one mechanism. Consequent to the pathogenic primacy of cellular prion protein (PrP^c)-to-scrapie PrP^c (PrP^sc) conversion, most reported treatments appear to directly target this replication process, although various other strategies, such as depletion of reaction substrates and abrogation of downstream effector pathways, have been utilized. Many factors, including experimental design, militate against reliable extrapolation of study results to the routine clinical setting or limit easy translational application to human disease. Notably problematic are approaches wherein benefit has been shown but the treatment was initiated before, at or soon after inoculation of experimental animals.

Keywords::

• amyloid
• antibiotic
• antioxidant
• Creutzfeldt–Jakob disease
• immunization
• pentosan polysulfate
• quinacrine
• RNA interference
• therapy

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

These diseases can arise genetically or be acquired after contact with infected tissue but the majority (∼85%) of cases have an origin that is yet to be determined and are classified as sporadic.

BSE: Bovine spongiform encephalopathy; CJD: Creutzfeldt–Jakob disease; CWD: Chronic wasting disease of deer, elk and moose; FFI: Fatal familial insomnia; gCJD: Genetic Creutzfeldt–Jakob disease; GSS: Gerstmann–Sträussler–Scheinker syndrome; iCJD: Iatrogenic Creutzfeldt–Jakob disease; TME: Transmissible mink encephalopathy; vCJD: Variant Creutzfeldt–Jakob disease resulting from injestion of BSE-contaminated products.