Study Rationale: Although Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, no drugs are currently available to treat or prevent the condition because the processes that underly its development and progression are poorly understood. Intestinal inflammation is believed to play a role in the development of certain types of PD. However, no causal inflammatory processes have been identified to facilitate developing novel therapies. In this study, we will categorize subtypes of PD based on genetic risk, levels of gut inflammation and intestinal bacterial composition, and we will identify specific inflammatory processes involved in PD.
Hypothesis: We hypothesize that a combination of genetic, inflammatory, and microbial biomarkers will help us categorize subtypes of PD, facilitating the development of personalized therapies. We also hypothesize that genes involved in the development of PD and other immune diseases could serve as novel targets to treat or prevent PD.
Study Design: We will use existing genetic data to calculate an inflammatory genetic score in people with PD recruited for other 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 individuals and correlate these measurements with disease progression. Lastly, we will compare genomic data from the brains of people with PD with those from individuals with inflammatory bowel disease and identify the genes and biological processes that may lead to the development of novel PD drug targets.
Impact on Diagnosis/Treatment of Parkinson’s disease: The proposed study will help identify particular inflammatory processes involved in PD. This information can lead to the development of novel drug targets, or the repurposing of existing therapies aimed at reducing inflammation in other immune diseases, as promising therapeutics for PD and other neurodegenerative diseases.
Next Steps for Development: Novel targets and biomarkers will be validated in experimental studies. Also, we will use large patient registries to assess whether existing drugs that target the inflammatory processes we find to be associated with PD subtypes lower PD risk in the general population.