Objective/Rationale:
The objective of this research is to determine whether epigenetic factors play a role in the development of sporadic Parkinson’s disease. Epigenetic factors are chemical modifications of the genome or its regulatory proteins that do not change the underlying genomic sequence of an organism. Epigenetic changes can occur in response to aging, hormonal factors, as well as various other environmental influences, which have also been implicated in the development of PD.
Project Description:
Epigenetic modifications at the genomic level can be measured by a specific chemical conversion reaction. Epigenetically modified DNA will resist the conversion, whereas unmodified genetic material will be altered. Specific genes, namely Alpha-synuclein and Parkin, which are implicated in PD, will be tested for these epigenetic modifications in blood of patients with PD and healthy controls. In addition, using an enzyme assay that is sensitive to the chemical modifications, we will be able to measure epigenetic changes at a genome-wide level and compare this in the same patient/control group.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The potential relevance for this work is that epigenetic modifications could prove the "missing link" between environmental risk factors and the development of PD. Epigenetic factors could also explain, at least in part, the striking clinical differences observed in sporadic PD like age at onset and progression. If a link is established, this could open up new avenues for therapeutic intervention targeting specifically epigenetic modifications. Furthermore, epigenetic marks in blood could lead to the development of biomarkers or tools to predict whether or not a person will develop PD.
Anticipated Outcome:
The expected outcome of these studies is that we might identify differences in the epigenetic fingerprint in PD patients versus controls. Since epigenetic changes are a novel concept for a risk and disease modifying mechanism in PD that has not been tested to date, positive as well as negative results would greatly advance our understanding of PD and foster future research efforts.