Study Rationale: The instructions needed to govern the function of living things are stored in their cells’ DNA. In cell types that divide, such as blood or skin, DNA checked for damage and repaired each time a cell divides. Neurons, however, never divide—so their DNA therefore remains the same for the entire life of the individual. Over this life span, neuronal DNA may become damaged by a variety of factors, including the natural byproducts of cell activity. Accumulation of DNA damage is one of the mechanisms responsible for aging, which is a major risk factor for Parkinson’s disease (PD).
Hypothesis: We hypothesize that people with PD will show an increased accumulation of DNA damage compared to healthy individuals of comparable age, and that these enhanced levels of DNA damage will contribute to PD progression and disease severity.
Study Design: We will analyze a large set of data obtained from blood samples available to The Michael J. Fox Foundation. Using this data, we will identify a molecular fingerprint—a distinctive pattern of biological molecules—that reflects an accumulation of DNA damage. This analysis will be based on computational methods of already existing data, an approach known as bioinformatics. We will also correlate the magnitude of this signature with disease severity and rate of disease progression.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this study would provide a tool for diagnosing and predicting PD progression and provide guidance for the development of new therapeutic approaches—for example, calorie restriction, an intervention that reduces the burden of DNA damage.
Next Steps for Development: Future experiments will involve studies in biological systems, such as neurons derived from people with PD or preclinical PD models, to further validate the outcome of this study.