Abstract

1) We and our collaborators have screened multiple anti-sense oligonucleotides for efficacy in reducing PrPC expression in the brain tissue of mice and in tissue cultures cells. The best candidates have proven to significantly reduce PrPC mRNA and protein expression in the brains of mice animals for extended periods of time after treatment. They also reduce the accumulation of PrPSc in scrapie-infected tissue culture cells. Both prophylactic and post-exposure treatments of mice inoculated with scrapie are ongoing.

  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 #
1ZIAAI001087-08
Application #
9560561
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
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  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
Hopping, Gene; Kellock, Jackson; Barnwal, Ravi Pratap et al. (2014) Designed ?-sheet peptides inhibit amyloid formation by targeting toxic oligomers. Elife 3:e01681
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; 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