Identification of Genetic Signatures in the Blood as Biomarkers for Parkinson's Disease

Study Rationale:
Epigenetic processes (changes in gene expression), such as DNA methylation (mechanism that cells use to control gene expression), ensure proper functioning of genetic materials in cells. Our previous studies found abnormal DNA methylation in blood samples from individuals with Parkinson's disease (PD). These changes may be associated with the disease and may also serve as potential biomarkers of PD. Biomarkers are molecules that can be used to track disease activity and can be easily measured from body tissues, such as blood. Biomarkers represent a promising diagnostic tool to aid in the earlier diagnosis of PD, in the tracking of disease progression and in determining whether new treatments are effective. However, there are no known biomarkers for PD, despite extensive efforts to identify them.

Hypothesis:
Our goal is to study changes in DNA methylation in a large group of participants with PD to discover a specific signal that could be used as a biomarker for this disease.

Study Design:
We will compare the pattern of DNA isolated from blood samples from 200 participants with PD and 200 healthy participants from the Harvard Biomarkers Study. We will investigate more than 450,000 markers in the genome. Once we detect the genes that have the greatest number of changes in the PD samples, we will select the ones that can better differentiate an individual with PD from an individual without PD to generate a diagnostic panel. We will repeat the study with blood samples obtained two years later to monitor how this signal changes as the disease progresses.

Impact on Diagnosis/Treatment of Parkinson's Disease:
Proper diagnosis of PD is usually achieved when motor disturbances are evident. However, by that time, many cells have already been lost. Our work aims to identify a unique molecular signature of PD that might help with an accurate diagnosis that can be easily performed on a blood sample. If DNA alterations are evident during the first stages of disease progression, this feature might serve as an early diagnostic tool.

Next Steps for Development:
Once we identify a set of markers that are highly specific to people with PD or that are predictive of the rate of PD progression, we will validate the performance of the panel on an independent group of cases. We will then seek paths to develop a diagnostic test that can be used in the clinic.

Additional Support:
The Michael J. Fox Foundation would like to acknowledge the generous contribution of the KiMe Fund as a lead supporter providing funding for this project.