Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie.
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.
Solassol
Jérôme
J
Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Crozet
Carole
C
Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Perrier
Véronique
V
Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Leclaire
Julien
J
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
Béranger
Florence
F
Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France.
Caminade
Anne-Marie
AM
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
Meunier
Bernard
B
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
Dormont
Dominique
D
Service de Neurovirologie, CEA, CRSSA, EPHE, BP 6, 92265 Fontenay aux Roses cedex, France.
Majoral
Jean-Pierre
JP
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France.
Lehmann
Sylvain
S
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.
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*
D000890:Anti-Infective Agents; D018620:PrPSc Proteins; D011328:Prions