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Nanomedicine for prion disease treatment

New insights into the role of dendrimers

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Pages 198-202 | Received 06 Mar 2013, Accepted 24 Mar 2013, Published online: 10 Apr 2013
 

Abstract

Despite their devastating impact, no effective therapeutic yet exists for prion diseases at the symptomatic stage in humans or animals. Progress is hampered by the difficulty in identifying compounds that affect PrPSc and the necessity of any potential therapeutic to gain access to the CNS. Synthetic polymers known as dendrimers are a particularly promising candidate in this area. Studies with cell culture models of prion disease and prion infected brain homogenate have demonstrated that numerous species of dendrimers eliminate PrPSc in a dose and time dependent fashion and specific glycodendrimers are capable of crossing the CNS. However, despite their potential a number of important questions remained unanswered such as what makes an effective dendrimer and how dendrimers eliminate prions intracellularly. In a number of recent studies we have tackled these questions and revealed for the first time that a specific dendrimer can inhibit the intracellular conversion of PrPC to PrPSc and that a high density of surface reactive groups is a necessity for dendrimers in vitro anti-prion activity. Understanding how a therapeutic works is a vital component in maximising its activity and these studies therefore represent a significant development in the race to find effective treatments for prion diseases.

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Disclosure of Potential Conflicts of Interest

No potential conflict of interest was disclosed.

Acknowledgments

This work was supported by University College Dublin, the Irish Research Council for Science, Engineering and Technology (IRCSET) the European Union (Dendrimers in Biomedical Applications—COST TD0802, Neuroprion—FOOD-CT-2004–506579), the Irish Department of Agriculture, Food and Rural Development (FIRM 01-R&D-D-160), the Saxon Ministry for Science and Art and The German Ministry for Education and Science, as well as the DFG SFB 596 (to Jorg Tatzelt).

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