There is a great need to develop new, readily accessible biomarkers — objective measures of disease — from biofluids (blood, urine, saliva or cerebrospinal fluid) for early diagnosis and treatment of Parkinson’s disease (PD). However, to date, no successful diagnostic tests based on such biomarkers have been developed. To overcome the challenges preventing the discovery of biofluid-based biomarkers, we propose to study the phosphorylated proteins, which have chemical phosphate attached, in extracellular vesicles (EVs) — small sacks released by cells as means of communication — in urine and cerebrospinal fluid (CSF). Analysis of phosphorylated proteins in EVs could offer exceptionally useful information and provide significant value given the important role of protein LRRK2, which can attach phosphate to other proteins, in Parkinson’s disease.
We propose to analyze regular and phosphorylated proteins in biosamples from people with PD using our EVtrap technology for quick and efficient capture of EVs from urine. We will analyze 106 urine samples available through the MJFF-led LRRK2 Cohort Consortium, which brought research groups together to speed efforts to move LRRK2 toward therapeutic relevance for patients. Regular and phosphorylated proteins will be analyzed using powerful technology called LC-MS/MS. Because this sample cohort has been uniquely selected for in-depth analysis and comparison of genes and function of LRRK2 in PD, we will focus our study particularly on LRRK2 and proteins it modifies with phosphate. We aim to discover new biomarkers with a potential to enable easy non-invasive approach to early PD diagnosis.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The current approaches to the diagnosis of Parkinson’s are imperfect and could be improved. In addition, PD is typically diagnosed at a late stage, when the symptoms are apparent and treatment has limited effectiveness. Tools for diagnosing PD at a very early stage non-invasively (i.e., through a urine test) would significantly expand the potential for successful PD treatment.
We expect this project to identify new potential biomarkers in the extracellular vesicles in the urine and further uncover the role of LRRK2 in Parkinson’s disease.