title: Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie.
abstract: Over the last 30 years, many drugs have been tested both in cell culture and in vivo for their ability to prevent the generation of prions and the development of transmissible spongiform encephalopathies. Among the compounds tested, dendrimers are defined by their branched and repeating molecular structure. The anti-prion activity of new cationic phosphorus-containing dendrimers (P-dendrimers) with tertiary amine end-groups was tested. These molecules had a strong anti-prion activity, decreasing both PrP(Sc) and infectivity in scrapie-infected cells at non-cytotoxic doses. They can bind PrP and decrease the amount of pre-existing PrP(Sc) from several prion strains, including the BSE strain. More importantly, when tested in a murine scrapie model, the dendrimers were able to decrease PrP(Sc) accumulation in the spleen by more than 80 %. These molecules have a high bio-availability and therefore exhibit relevant potential for prion therapeutics for at least post-exposure prophylaxis.
authors.affiliation: Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Solassol
authors.affiliation: Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Crozet
authors.affiliation: Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Perrier
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Leclaire
authors.affiliation: Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Béranger
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.affiliation: Service de Neurovirologie, CEA, CRSSA, EPHE, BP 6, 92265 Fontenay aux Roses cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Dormont
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Majoral
authors.affiliation: Laboratoire de Biochimie, Hôpital St Eloi, 80 av. A. Fliche, 34295 Montpellier Cedex 5, France.|Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011328:Prions / Q000037:antagonists & inhibitors*; D012608:Scrapie / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D018620:PrPSc Proteins; D011328:Prions