GAin-PD: Validation of bacterial-derived anti-inflammatory mediators in gut-first Parkinson disease

Overview

Project Summary

Parkinson disease (PD), the second most common neurodegenerative disease, is fast growing and is presently a major public health problem partly as result of a rapid and substantial rise in global life expectancy and the existence of increasingly aged populations. Currently available treatments show only modest symptomatic efficacy, leaving an unmet medical need for new and effective therapies. For more than thirty years it has been  understood that inflammatory changes occur in the blood and brain of PD patients, but only in the last few years has inflammation been viewed as part of the progressive nature of the disease and not just a result of the disease. Additionally, recent data highlights that the changes in the bacterial composition in the gut of people with PD may trigger inflammation in the gut which fuels the disease. A seminal hypothesis was recently proposed for PD etiology where gut dysbiosis could trigger PD if systemic inflammation acting as a facilitator was present. We propose that averting gut and systemic inflammation will prevent the progression of the pathology to the CNS. Nevertheless, all clinical trials using conventional anti-inflammatory drug failed to arrest or delay PD progression. Our project adopts a preclinical trial study since we aim to validate new promising anti-inflammatory candidates. 

Main Goals

1) To determine how new anti-inflammatory mediators avert motor behaviour alterations and SNpc and DMV (dorsal motor nucleus of the vagus) TH+ cell loss in gut-first gmPD mice); 

2) To determine the influence of anti-inflammatory mediators in gut inflammation and barrier integrity;

3) To identify intestinal immune pathways modulated by anti-inflammatory mediators;

4) To evaluate the effects of this new anti-inflammatory strategy on BBB leakage, mitochondrial fragmentation and microglia activation; 

5) To understand how neuronal immune control is related to the production/aggregation of aSyn.

Project Details