Funded Studies
Study Rationale: Cannabinoids — substances derived from the cannabis plant — have demonstrated neuroprotective properties useful for the treatment of neurodegenerative disorders. Although these effects are believed to be mediated by interactions with classic cannabinoid receptors, recent studies have provided experimental evidence for the contribution of additional, non-classic receptors. Such is the case for GPR55, an orphan receptor that was recently shown to be related to the body’s endocannabinoid system. This receptor may be particularly relevant in Parkinson’s disease (PD) because it plays a role in the control of movement and is abundant in the brain region most affected by PD.
Hypothesis: Our hypothesis is that activating GPR55 may delay disease progression in PD. In this research proposal, we investigate this hypothesis using preclinical PD models.
Study Design: We will begin by analyzing how the target receptor, GPR55, is altered in damaged neuronal structures over the course of progression of pathology in preclinical mouse models of PD and in postmortem samples from people with PD. Next, we will assess whether already existing and novel compounds that bind to GPR55 can delay or arrest disease progression in the preclinical models. Lastly, we will induce parkinsonism in mice genetically deficient in GPR55 and monitor the changes in the progression of pathology.
Impact on Diagnosis/Treatment of Parkinson’s disease: The lack of efficacious strategies to delay or arrest disease progression in PD demands urgent action to identify new targets for which pharmacological management may have neuroprotective effects. If successful, this study would situate GPR55 as a novel target for potential novel neuroprotective agents.