Study Rationale:
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Currently, no drugs are available to treat or prevent the disease because the processes leading to PD development are still poorly understood. There is growing appreciation for the gut-brain connection, suggesting that intestinal inflammation can play a role in the development of certain types of Parkinson’s. However, no causal inflammatory processes have been identified to allow for developing novel therapies. Therefore, the goal of this study is to determine subtypes of Parkinson’s based on the genetic risk, levels of gut inflammation and bacterial composition and identify particular inflammatory processes involved in Parkinson’s.
Hypothesis:
We hypothesize that a combination of genetic, inflammatory and microbiome (types of bacteria in the gut) biomarkers will help identify certain subtypes of Parkinson’s leading to personalized therapies. We also hypothesize that genes involved in the development of Parkinson’s and other immune diseases could serve as novel targets to treat or prevent PD.
Study Design:
First, we will use existing genetic data to calculate an inflammatory genetic score in Parkinson’s patients recruited for various studies and identify whether those with the highest and lowest scores have a particular course of the disease. We will also measure the levels of gut inflammation and bacterial diversity in newly recruited Parkinson’s patients and correlate them with their disease progression. Lastly, we will overlap genomic data from living patient brains and postmortem brains with those from patients with inflammatory bowel disease and identify the genes and biological processes that may lead to the development of novel Parkinson’s drug targets.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The proposed study will help identify particular inflammatory processes involved in Parkinson’s. This information can lead to the development of novel drug targets or repurposing of existing therapies used to treat other immune diseases aimed at reducing inflammation, as a promising interventional goal for Parkinson’s.
Next Steps for Development:
Novel targets and biomarkers will be validated in experimental studies. Also, we will use large patient registries to test whether existing drugs targeting the inflammatory processes, which we found to be associated with Parkinson’s types, prevent PD risk in the general population.