Back
Full-text
Journal article

A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion toxicity.

  • Bardelli M Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Frontzek K Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Simonelli L Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Hornemann S Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Pedotti M Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Mazzola F Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Carta M Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Eckhardt V Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • D'Antuono R Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Virgilio T Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • González SF Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
  • Aguzzi A Institute of Neuropathology, University of Zurich, Zurich, Switzerland.
  • Varani L Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.
Show more…
  • 2018-10-02
Published in:
  • PLoS pathogens. - 2018
Animals
Antibodies, Bispecific
Cells, Cultured
Cerebellum
Complementarity Determining Regions
Immunotherapy
Mice
Mice, Transgenic
Prion Diseases
Prion Proteins
Prions
English Antibodies to the prion protein, PrP, represent a promising therapeutic approach against prion diseases but the neurotoxicity of certain anti-PrP antibodies has caused concern. Here we describe scPOM-bi, a bispecific antibody designed to function as a molecular prion tweezer. scPOM-bi combines the complementarity-determining regions of the neurotoxic antibody POM1 and the neuroprotective POM2, which bind the globular domain (GD) and flexible tail (FT) respectively. We found that scPOM-bi confers protection to prion-infected organotypic cerebellar slices even when prion pathology is already conspicuous. Moreover, scPOM-bi prevents the formation of soluble oligomers that correlate with neurotoxic PrP species. Simultaneous targeting of both GD and FT was more effective than concomitant treatment with the individual molecules or targeting the tail alone, possibly by preventing the GD from entering a toxic-prone state. We conclude that simultaneous binding of the GD and flexible tail of PrP results in strong protection from prion neurotoxicity and may represent a promising strategy for anti-prion immunotherapy.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/298559
Statistics
Document views: 34 File downloads:
  • Full-text: 0