Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title: Imaging Blood Brain Imaging Dysfunction in Parkinson's Disease

Status Completed

Clinical Trial Summary

The purpose of this study is to evaluate the blood brain barrier in the striatum of patients that have other types of movement disorders compared to patients with Parkinson's Disease that are receiving similar treatment, to determine if a there is a disruption of the blood brain barrier in patients with Parkinson's Disease.

Clinical Trial Description

Parkinson's disease (PD) is the most common neurodegenerative movement disorder of aging. Its cause is unknown. Current evidence supports a stress-diathesis model of pathogenesis whereby some yet-to-be identified environmental trigger conspires with a permissive genetic background to initiate the disease process. Based on neuropathological observations in other neurodegenerative diseases, such as chronic traumatic encephalopathy where pathological protein aggregates form in close association with damaged blood vessels, investigators have hypothesized that the environmental trigger resides in the bloodstream. As a corollary of this hypothesis, investigators propose that the PD pathological process begins in the brain of affected individuals only after disruption of the blood brain barrier (BBB), thereby allowing access of the inciting agent to nigrostriatal axon terminals in the neostriatum. This forms the foundation for the investigators' hypothesis that the BBB in the neostriatum of PD patients is disrupted. Indeed, in a post-mortem study, investigators demonstrated histopathological evidence for significant striatal BBB disruption in sections of striatum from PD subjects relative to age-matched controls. Critics of this study indicate that post-mortem effects may result in artefactual disruption of the BBB, calling into question the validity and relevance of this potentially important finding to PD pathogenesis and progression. Therefore, investigators are performing this imaging study of live PD patients as a follow-up of their convincing post-mortem study to definitively establish whether BBB dysfunction is a feature of PD.

The neostriatal BBB is dysfunctional in PD patients relative to controls and this can be demonstrated by significantly increased parenchymal enhancement on magnetic resonance imaging (MRI).

The results of these studies could have important implications for the understanding of PD pathogenesis. There is emerging evidence that the key pathogenetic event in PD pathogenesis, aggregation of alpha-synuclein, begins within the axon terminals of neurons. The neurons most severely affected in PD reside in the substantia nigra and project to the neostriatum. Demonstrating disruption of the BBB in the PD striatum would render nigrostriatal axon terminals susceptible to a blood-borne disease trigger and allow researchers to generate hypotheses regarding the identity of this trigger. Immune/inflammatory candidates are particularly attractive in this regard. The results this study may also have therapeutic implications. For example, if alpha-synuclein disaggregating agents achieve therapeutic utility in the coming years, our studies may indicate that such agents may be capable of accessing nigrostriatal axon terminals without requiring pharmaceutical or mechanical disruption of the BBB. ;

Related Conditions & MeSH terms

• Movement Disorders
• Parkinson Disease
• Parkinson's Disease

• NCT number: NCT02605161
• Study type: Observational
• Source: Ottawa Hospital Research Institute
• Status: Completed
• Start date: November 2015
• Completion date: September 8, 2020