Team Hardy

Study Rationale: The progression of Parkinson’s disease is very variable, with some individuals having a rapid course and others having a longer and more benign course. Team Hardy believes that by understanding the genetics and the mechanistic basis of this variability, they will be able to design therapies to slow Parkinson’s progression. Team Hardy has already found that GBA mutations lead to a rapid disease course and that LRRK2, linked to familial forms of Parkinson’s, influences the course of parkinsonism in another disease: progressive supranuclear palsy. They will test whether modulating these enzymes influences the course of pathology spread in a pre-clinical model of progression as a validation of this approach to disease treatment.

Hypothesis: Team Hardy wants to find and understand the genes that are involved in Parkinson’s progression and test whether modulating them pharmacologically influences disease progression.

Study Design: Through genetic analysis, Team Hardy will find genes that influence the progression of parkinsonism, and then assess the mechanisms by which they affect disease development. They have already found that GBA and LRRK2 influence clinical rates of decline so Team Hardy will test, in a mouse model of pathology progression, whether inhibiting these enzymes influences pathology spread and thereby develop a relevant platform to test drugs for slowing disease progression.

Impact on Diagnosis/Treatment of Parkinson’s Disease: This research will impact Parkinson’s care in three ways. First, by understanding the genetics of rate of decline, these data can be factored into clinical trial design and possibly more generally into clinical practice. Second, the identification of pathways involved in disease progression is likely to reveal further drug targets. And thirdly, the testing of GBA and LRRK2 inhibitors in a mouse model of disease progression will test this as a valid approach to treatment development.