Study Rationale: Accumulative evidence suggests a strong connection between the brain and the gut, with chronic intestinal inflammation being linked to an increased risk of Parkinson’s disease (PD). However, limited access to human tissue is a significant roadblock to further explore potential biomarkers of PD in the gut. These biomarkers can help identify individuals at risk of the disease and design novel strategies for disease prevention. The goal of this study is to advance techniques that will allow the utilization of archived intestinal tissue from PD patients to characterize the top biological pathways associated with PD development, LRRK2 kinase activity and intestinal inflammation (Paneth cell function).
Hypothesis: We hypothesize that PD diagnosis are associated with significant changes in the LRRK2 kinase signaling pathway and Paneth cell pathology in the gut. We also hypothesize that patients with inflammatory bowel disease (IBD), known to have a higher risk of PD, will have elevated levels of urine bis(monoacylglycero)phosphate (BMP), a sensitive biomarker of PD, which may help stratify patients at increased risk of PD.
Study Design: We will identify PD patients who underwent gut surgeries or colonoscopies at the Mount Sinai Medical Center and use their archived intestinal samples to profile biological pathways contributing to PD and IBD risk. Given recent findings demonstrating abnormal Paneth cell in engineered mice with the genetic variant associated with PD (Lrrk2 G2019S), we also plan, for the first time, to isolate and characterize Paneth cells in the gut of PD patients. Lastly, we will test whether elevated urine BMP levels correlate with intestinal inflammation and could serve as an early biomarker of PD in IBD patients.
Impact on Diagnosis/Treatment of Parkinson’s disease: This project holds potential to inform novel strategies for PD risk stratification and prevention by identifying early biomarkers of PD development in the intestinal tissue that may precede the onset of PD.
Next Steps for Development: If successful, this study will identify early biomarkers of PD that can be detected in the gut or urine of individuals at high risk of developing PD before the disease is established. Also, newly developed techniques will allow to use archived intestinal samples for future research and clinical PD risk stratification, as well as help design novel strategies for disease prevention