Study Rationale:
As new, targeted therapies for Parkinson's disease (PD) enter clinical trials, biomarkers -- objective measures of disease --become increasingly important as tools for matching people with PD with the most appropriate treatment. In this study, we aim to develop two different biomarkers: one measuring the activation status of protein LRRK2 -- a leading contributor to the inherited form of PD -- and the other measuring dysfunction of lysosomes, which are small sacks responsible for breaking down cellular waste. We plan to use blood and urine samples donated by people with Parkinson's, and in particular by people who carry disease-causing mutations (changes) in proteins LRRK2, VPS35 and GBA.
Hypothesis:
In this study, we aim to develop, compare and correlate PD biomarkers reflecting LRRK2 activation status and lysosomal dysfunction in people with inherited Parkinson's linked to genetic changes in VPS35, LRRK2 and GBA as well as in people with Parkinson's without a known cause.
Study Design:
We will collect urine and blood samples from 40 donors. Within 24 hours of blood collection, three different types of blood cells (neutrophils, monocytes and peripheral blood mononuclear cells) will be collected from the blood samples. A small fraction of each cell type as well as urine will be analyzed to determine lysosomal function. This analysis will be done in the United States, while LRRK2 activation will be analyzed in Dundee, United Kingdom. Overall data analysis will then be performed in Dundee.
Impact on Diagnosis/Treatment of Parkinson's Disease:
This study will help us determine the usefulness of the two biomarkers for selecting people with Parkinson's for clinical studies, which is important in the light of emerging targeted therapies.
Next Steps for Development:
The proposed study includes a small numbers of participants and will assist in designing a larger study with more participants, specifically, by determining the protocols to be used in the future.