Study Rationale:
Because Parkinson's disease (PD) is a complex disease, it is difficult to accurately diagnose and treat. Biomarkers -- disease indicators that are critical missing links in the search for better Parkinson's treatments -- are useful in tracking disease progression and measuring the success of treatment. However, reliable Parkinson's disease biomarkers are still lacking, despite much progress in research to find them. Development of a biomarker that aids in diagnosis of people at the earliest stages of PD or those at high risk for developing the disease could improve current treatment strategies.
Hypothesis:
Our study has three primary goals. First, we aim to provide a high-quality data set to the research community as a resource to use in their own studies. This data set will contain information on DNA methylation, a mechanism of turning off genes, including genes linked to the inherited form of PD. The data set will be based on samples from the Parkinson's Progression Markers Initiative (PPMI), The Michael J. Fox Foundation's landmark clinical study to find biomarkers. Second, we aim to test previously identified Parkinson's-associated patterns of methylation using samples from this study. Finally, we aim to develop a set of reliable biomarkers based on methylation of DNA that varies with disease progression.
Study Design:
We will analyze blood samples from the PPMI study donated over the course of three years by people with idiopathic PD -- a form of disease with an unknown cause --and by healthy people. This will allow us to describe DNA methylation and compare it to clinical measures of disease. In addition, we will study a set of samples from people who have changes (mutations) in the LRRK2 gene including people diagnosed with PD and those without symptoms. Importantly, we will produce the first genome-wide DNA methylation maps describing methylation across the entire cell's DNA in people with the early signs of Parkinson's. This part of the study may identify, for the first time, methylation that signals the onset of PD. All data will be uploaded to the PPMI database for other researchers developing biomarkers for PD to access and use.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If successful, these studies could provide a method of predicting PD in people at risk and enhance clinical trials of new therapeutics by providing a biomarker based on DNA methylation to track disease progression and measure efficacy of new treatments.
Next Steps for Development:
We hope to confirm these results in other studies and to use a DNA methylation test in the clinic to help diagnose Parkinson's disease early and support clinical trials by evaluating therapeutic efficacy.