Evaluation of LRRK2 Inhibition in a Pre-clinical Model of Parkinson's Disease

Study Rationale:

The most common genetic cause of Parkinson's disease (PD) is mutations in the LRRK2 gene. Variations in the LRRK2 gene are associated with non-genetic PD as well. New drugs are being identified to reverse the effects of LRRK2 activity and related pathology. To this end, the current study will investigate the effects of a novel LRRK2 kinase inhibitor in pre-clinical models with pathology like human PD.

Hypothesis:

LRRK2 kinase inhibition reverses or prevents death of dopamine neurons in a pre-clinical model of PD.

Study Design:

Pre-clinical models with progressive degeneration of dopaminergic neurons will receive daily treatment with LRRK2 inhibitor for 20 weeks. Behavior will be assessed each month and the ability of the treatment to protect dopamine neurons will be evaluated by post-mortem analysis of brain tissue.

Impact on Diagnosis/Treatment of Parkinson's Disease:

LRRK2 kinase inhibitors have not yet been used in the treatment of PD. This study will provide pre-clinical evidence as to whether such treatment strategies should be pursued.

Next Steps for Development:

Pre-clinical success of a LRRK2 inhibitor will pave the way forward for other drugs of a similar class to be further evaluated and developed for use in clinical trials.