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MRC Prion Unit
From fundamental research to prevention and cure

Small molecule therapeutics

This is a major collaborative project with GlaxoSmithKline (GSK) directly funded by the Department of Health with the aim of developing an effective small molecule therapeutic for the treatment of prion disease in humans. The unique academic-industrial collaboration assembled for this project, bringing together one of the world’s leading academic centres of expertise in prion biology and neurodegeneration with one of the world’s leading pharmaceutical companies not only provides an unparalleled combination of expertise to tackle prion disease therapeutics, but also allows this to be performed at a fraction of normal commercial costs.

Molecule bound cellular form
We have developed a binding assay to look for molecules which bind to (and thereby stabilise) the cellular form of the prion protein (figure 1). Binding to the cellular form of the protein should prevent its conversion to the pathogenic form of the protein (figure 2). The binding assay has been used to screen over one million drug-like compounds from GSK compound collection. Hits from the initial screen have been characterised in a variety of cellular and biophysical binding assays: NMR, circular dichroism, SPR (Biacore). We have also screened compounds directly in cellular models of prion disease, and are now engaged in a major medicinal chemistry program to optimise the lead compounds identified from screens prior to testing them in disease models.
Prevent conversion of pathogenic form

Recent Publications:

Preventing prion pathogenicity by targeting the cellular prion protein.
Nicoll AJ, Collinge J.
Infect Disord Drug Targets. 2009 Feb;9(1):48-57. 

MRC Prion News