Neural Network Imaging Analysis in Parkinson’s Disease Associated with Parkin Mutation

Study Rationale: Clinical imaging biomarkers are desperately needed to provide a non-invasive means of assessing therapeutic efficacy in clinical trials for Parkinson’s disease (PD). Recent studies using neural network imaging analysis have demonstrated a PD-related pattern (PDRP) and PD cognitive pattern (PDCP) that correlates with disease progression, findings validated by functional MRI imaging. Individuals with PD associated with LRRK2 and GBA mutations have demonstrated a PDRP/PDCP closely related to the patterns evidenced in idiopathic PD. In this study, we will evaluate the PDRP/PDCP patterns of people with Parkin-based PD, who have not yet been analyzed using this technique.

Hypothesis: Individuals with Parkin-PD present with a spatially restricted loss of dopamine-producing neurons and little to no cortical involvement. We therefore hypothesize that this population will demonstrate a PDRP that is similar to people with idiopathic PD but will lack a PDCP component.

Study Design: People with Parkin-PD and healthy controls will be scanned using standard FDGPET imaging and fMRI methods. The resulting scans will be the basis for determining a Parkin-specific PDRP/PDCP using established algorithms. We will also examine Parkin-PD network architechture from a structural perspective using diffusion tensor imaging. Parkin datasets will be compared to control, idiopathic, LRRK2 and GBA patterns to assess PDRP pattern overlap and distinction, as well as any structural changes unique to Parkin-PD.  

Impact on Diagnosis/Treatment of Parkinson’s Disease: We will deliver a comprehensive neural network imaging analysis of people with Parkin-PD. This data will provide two critical deliverables: imaging tools for therapeutic testing in a highly relevant, yet underserved, genetic population and definitive assessment of the similarity of Parkin-PD to the broader population of idiopathic PD.

Next Steps for Development: Determination of a Parkin-specific pattern, or confirmation of the established PDRP in those with Parkin-PD, will provide a clinical imaging tool for assessing therapeutic efficacy. Application of this technology to additional PD cohorts can validate specific imaging technology for use as an imaging companion to the UPDRS scoring system.

Trial Phase: 12 months