Targeting glucocerebrosidase for disease-modifying treatments in Parkinson’s disease

Anthony H.V. Schapira (UK), David Park (Canada), Donato Di Monte (Germany) and Fabio Blandini (Italy)

Parkinson disease is a progressive neurodegenerative disorder treatment for which is limited to improving symptoms and there is an urgent need to develop drugs that slow progression. It has recently been shown that mutations of the glucocerebrosidase gene result in a very significant increased risk for PD, and that approximately 10% of patients carry such mutations. Our project is designed to explore the mechanisms by which the mutations increase the risk for PD and to test candidate drugs that reverse the biochemical changes induced by the mutations. We hypothesise that this will result in a reduction in alpha-synuclein levels, the protein that builds up in Parkinson neurons and that is thought to be at the centre of the degenerative process. The candidate drugs will first be tested in cell and animal models of the mutations as part of this international collaboration in confirming this proof of principle. Positive results will lead to drug development for patients.