Archives of Virology

, Volume 154, Issue 9, pp 1539–1544

ST1859 reduces prion infectivity and increase survival in experimental scrapie

  • Laura Colombo
  • Paola Piovesan
  • Orlando Ghirardi
  • Mario Salmona
  • Gianluigi Forloni
Brief Report

DOI: 10.1007/s00705-009-0471-0

Cite this article as:
Colombo, L., Piovesan, P., Ghirardi, O. et al. Arch Virol (2009) 154: 1539. doi:10.1007/s00705-009-0471-0

Abstract

On the basis of the structural homologies between ST1859 (1[(2-hydroxy-1-naphtyl)methyl]-2-naphthol) and the anti-prion agents and its anti-amyloidogenic activity, we tested whether this molecule altered the biochemical properties of aggregates formed in vitro by synthetic prion peptides and affected prion infectivity in experimental scrapie. Co-incubation of ST1859 with the peptides PrP 106–126 and PrP 82–146 reduced their fibrillogenic capacity and their resistance to digestion with protease K. Hamsters inoculated with the ST1859-treated homogenate showed a significant delay in the onset of clinical signs of disease and longer survival. Survival was also significantly longer in infected hamsters treated peripherally with ST1859 for the whole post-inoculation period until the onset of clinical symptoms. Similar results were found with the analogue ST1745. Our data indicate that ST1859 reduces prion infectivity and can exert a therapeutic effect in experimental scrapie.

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Laura Colombo
    • 1
  • Paola Piovesan
    • 2
  • Orlando Ghirardi
    • 2
  • Mario Salmona
    • 1
  • Gianluigi Forloni
    • 1
  1. 1.Istituto di Ricerche Farmacologiche “Mario Negri”MilanItaly
  2. 2.R&D Laboratory Sigma Tau s.p.a.RomeItaly