Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice

Fabio Moda, Chiara Vimercati, Ilaria Campagnani, Margherita Ruggerone, Giorgio Giaccone, Michela Morbin, Lorena Zentilin, Mauro Giacca, Ileana Zucca, Giuseppe Legname, Fabrizio Tagliavini

Research output: Contribution to journalArticle

Abstract

Prion diseases are caused by a conformational modification of the cellular prion protein (PrPC) into disease-specific forms, termed PrP Sc, that have the ability to interact with PrPC promoting its conversion to PrPSc. In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrPC region involved in the interaction with PrPSc thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrPSc in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding.

Original languageEnglish
Pages (from-to)383-390
Number of pages8
JournalPrion
Volume6
Issue number4
DOIs
Publication statusPublished - Sep 2012

Fingerprint

Prion Diseases
Prions
Scrapie
Brain
Antibodies
Proteostasis Deficiencies
Single-Chain Antibodies
PrPC Proteins
Anti-Idiotypic Antibodies
Peptide Hydrolases
Curing
Animals
Molecules
Therapeutics
Proteins

Keywords

  • AAV9
  • Immunotherapy
  • Monovalent antibody
  • Neurodegeneration
  • Prion disease

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Infectious Diseases
  • Cellular and Molecular Neuroscience

Cite this

Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice. / Moda, Fabio; Vimercati, Chiara; Campagnani, Ilaria; Ruggerone, Margherita; Giaccone, Giorgio; Morbin, Michela; Zentilin, Lorena; Giacca, Mauro; Zucca, Ileana; Legname, Giuseppe; Tagliavini, Fabrizio.

In: Prion, Vol. 6, No. 4, 09.2012, p. 383-390.

Research output: Contribution to journalArticle

Moda, F, Vimercati, C, Campagnani, I, Ruggerone, M, Giaccone, G, Morbin, M, Zentilin, L, Giacca, M, Zucca, I, Legname, G & Tagliavini, F 2012, 'Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice', Prion, vol. 6, no. 4, pp. 383-390. https://doi.org/10.4161/pri.20197
Moda, Fabio ; Vimercati, Chiara ; Campagnani, Ilaria ; Ruggerone, Margherita ; Giaccone, Giorgio ; Morbin, Michela ; Zentilin, Lorena ; Giacca, Mauro ; Zucca, Ileana ; Legname, Giuseppe ; Tagliavini, Fabrizio. / Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice. In: Prion. 2012 ; Vol. 6, No. 4. pp. 383-390.
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