Abstract

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 misfolded protein, called PrPres, in infected hosts. We and others previously had identified pentosan polysulfate, tannic acid, tetracycline HCl as strong blockers of PrPres accumulation. In this study, we compared prion infection rates among mule deer (Odocoileus hemionus) receiving pentosan polysulfate, tannic acid, tetracycline HCl, or no treatment 14 days before to 14 days after (dpi) oral inoculation with tonsil tissue homogenate. All deer were infected, but the rapid disease course (230-603 dpi) suggested our challenge was overwhelming and that the drugs were not able to protect against such a high-titered inoculum of CWD infectivity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001087-04
Application #
8555996
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2012
Total Cost
$191,339
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Ferreira, N C; Ascari, L M; Hughson, A G et al. (2018) A Promising Antiprion Trimethoxychalcone Binds to the Globular Domain of the Cellular Prion Protein and Changes Its Cellular Location. Antimicrob Agents Chemother 62:
Kellock, Jackson; Hopping, Gene; Caughey, Byron et al. (2016) Peptides Composed of Alternating L- and D-Amino Acids Inhibit Amyloidogenesis in Three Distinct Amyloid Systems Independent of Sequence. J Mol Biol 428:2317-2328
Ferreira, Natalia C; Marques, Icaro A; Conceição, Wesley A et al. (2014) Anti-prion activity of a panel of aromatic chemical compounds: in vitro and in silico approaches. PLoS One 9:e84531
Vieira, Tuane C R G; Cordeiro, Yraima; Caughey, Byron et al. (2014) Heparin binding confers prion stability and impairs its aggregation. FASEB J 28:2667-76
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
Hopping, Gene; Kellock, Jackson; Caughey, Byron et al. (2013) Designed Trpzip-3 ?-Hairpin Inhibits Amyloid Formation in Two Different Amyloid Systems. ACS Med Chem Lett 4:824-8
Wolfe, Lisa L; Kocisko, David A; Caughey, Byron et al. (2012) Assessment of prospective preventive therapies for chronic wasting disease in mule deer. J Wildl Dis 48:530-3
Taubner, Lara M; Bienkiewicz, Ewa A; Copié, Valérie et al. (2010) Structure of the flexible amino-terminal domain of prion protein bound to a sulfated glycan. J Mol Biol 395:475-90
Sim, Valerie L; Caughey, Byron (2009) Recent advances in prion chemotherapeutics. Infect Disord Drug Targets 9:81-91