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Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie

Jérôme Solassol^1,

Carole Crozet^1,

Dominique Dormont^3,

¹ Institut de Génétique Humaine du CNRS, 141 rue de la Cardonille, 34396 Montpellier, France
² Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse, France
³ Service de Neurovirologie, CEA, CRSSA, EPHE, BP 6, 92265 Fontenay aux Roses cedex, France
⁴ Laboratoire de Biochimie, Hôpital St Eloi, 80 av. A. Fliche, 34295 Montpellier Cedex 5, France

Correspondence
Sylvain Lehmann
Sylvain.Lehmann{at}igh.cnrs.fr

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.

Contributed equally to this work.

In memory of Professor Dominique Dormont.

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