High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals
Abstract
No effective treatments have been validated for the transmissible spongiform encephalopathies (TSEs) or prion diseases. To advance the rational basis for the search for anti-TSE therapeutics, we have developed a new unified mechanistic model for the activity of various classes of PrPSc inhibitors which is consistent with a considerable body of evidence from our laboratory and others. Based on this model, we have successfully developed a new potentially high-throughput screen for new anti-TSE compounds which is based on monitoring the ability of compounds to compete with the binding of a well-characterized anti- TSE compound (a PS-ON) to PrP-sen. Finally, we have discovered that combination drug treatments can substantially improve survival times of animals with established TSE infections of the central nervous system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2007
- Accession Number
- ADA475225
Entities
People
- Byron Caughey
- David Kocisko
Organizations
- National Institutes of Health