Development of a sensitive in vitro system for anti-alpha-synuclein aggregation drug screening

Aims

This project aims to demonstrate the use of a new in vitro technique which avoids the use of animals to screen a library of drugs approved for a range of diseases to test whether they might also be effective treatments for Parkinson's disease.

Background

Parkinson's disease is a neurodegenerative disease, without cure, which affects one person in every 500. Current treatments can only relieve symptoms, and do not stop the disease progressing. The aggregation of a protein called alpha synuclein is thought to have a role in the development of Parkinson's disease, so a way of testing which drugs can prevent this aggregation could lead to the development of more efficacious treatments.

Research details and methods

Drug libraries containing compounds already approved for use in other disease areas will be screened for their action against alpha synuclein using an alpha synuclein protein misfolding cyclic amplification system, published by Herva in 2014. 

The use of libraries of approved drugs means that all of the safety studies that require animal testing have already been done. After selecting the drugs that inhibit alpha synuclein aggregation, their efficacy and biological relevance will be assessed using existing and new cellular and mouse models of Parkinson's disease. 
 
This project will improve the knowledge about the mechanisms of alpha synuclein aggregation and accumulation in Parkinson's disease. It could produce results that could translate into disease modifying therapies slowing down or even stopping the progression of Parkinson's disease with minimal animal use.

Herva ME et al. (2014) Anti-amyloid compounds inhibit alpha-synuclein aggregation induced by Protein Misfolding Cyclic Amplification (PMCA). J Biol Chem. doi: 10.1074/jbc.M113.542340

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Fellowship

Status

Closed

Principal investigator

Dr Maria Eugenia Herva Moyano

Institution

University of Cambridge

Grant reference number

NC/K00199X/1

Award date

Oct 2013 - Sep 2015

Grant amount

£195,000