The transmissible spongiform encephalopathies (TSEs or prion diseases)are fatal untreatable neurodegenerative diseases such as scrapie, Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy and chronic wasting disease (CWD). TSE pathogenesis involves the accumulation of an abnormal protein, called PrPres, in infected hosts. We and others previously identified a variety of linear or branched sulfated polymers that are effective in inhibiting PrPres accumulation and slowing or prevent the progression of scrapie in experimental animals. However, these large charged polymers have difficulty crossing the blood-brain barrier to enter the brain after peripheral administration. We have therefore sought smaller molecules of this sort that might be effective PrPres inhibitors while having better bioavailability or lower toxicity in infected individuals. Toward this goal, we tested several sulfated cyclodextrins and found that some were excellent inhibitors of PrP-res accumulation in scrapie-infected tissue culture cells.

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