Study Rationale: “Retromer” is a molecular machine that regulates the trafficking of many proteins within a cell. While a dysfunction of Retromer is now known to be central in triggering and driving some cases of Parkinson’s disease, currently, there is no way to know which patient has retromer dysfunction. This project aims to validate a urine-based biomarker of retromer dysfunction in Parkinson’s disease, detectable in living patients.
Hypothesis: Based on previous studies, we hypothesize that we can identify and optimize specific biomarkers reflecting retromer dysfunction in different human biofluids, including blood and urine.
Study Design: Our previous studies identified proteins abnormally secreted from neurons into the spinal fluid and ultimately the bloodstream, acting as biomarkers of retromer dysfunction in the brain. However, it remains unknown if and how these biomarkers behave specifically in Parkinson’s disease. To address this question, this project will test these biomarkers in the blood and will expand our findings in urine of Parkinson’s disease patients.
Impact on Diagnosis/Treatment of Parkinson’s disease: Establishing biomarker of retromer dysfunction in Parkinson’s disease will not only improve diagnostic precision but also advance future therapeutic trials, particularly as retromer-based treatments are already being explored.
Next Steps for Development: After validating the retromer biomarker in this project in both blood and urine, the next phase will involve applying it to a broader and larger patient population—across various disease stages and known etiologies—to assess their specificity, sensitivity and accuracy.