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Funding from The Parkinson Alliance helped to finance the following Parkinson's research. Grantees were selected by scientific review committees of participating organizations. Updates will be posted, when available.
Project Title: Environmental and Genetic Determinants of Progression in a Community-Based Cohort
Principal Investigator(s): Beate Ritz MD, PhD
Objective/Rationale: Parkinson’s Disease (PD) is a progressive disease known for its decline in motor- and non-motor functions and symptoms. PD progression is unpredictable over the course of the disease. Within a few years of diagnosis, some patients become wheelchair bound, cognitively impaired, severely depressed, and/or experience many other non-motor symptoms. In contrast other patients are spared major motor and non-motor disabilities despite having the disease for several years. There is a notable knowledge gap regarding the genetic and environmental factors that contribute to or modify the progression of PD. We aim to address this critical need by exploring the contributions of environmental toxins, genetic and epigenetic factors, and gene-environment interactions to PD’s complex progression phenotype.
Project Description/Methods/Design: This proposal builds upon our rich existing resources and expanding our data on PD patients followed longitudinally in the largest community-based cohort. Since 2000, we have been conducting the Parkinson Environment-Gene (PEG) study in rural central California with the aim to characterize contributions of pesticides and genes on the onset of incident idiopathic PD. We followed 250 patients diagnosed 1998-2006 longitudinally until 2012. All patients were assessed for depression (GDS, SCID), cognitive decline (MMSE), non-motor symptoms (such as sleep, autonomic dysfunctions etc.), lifestyle, behavioral, and medical factors and provided biological samples at baseline. While 235 were re-examined for motor and non-motor function (mUPDRS), 185 were seen twice during follow-up. Follow-up exams were conducted on average 3 and 5 years after the baseline PEG exam. We later enrolled another large group of PD subjects (PEG2) and have been following this 2nd cohort longitudinally as with the 1st PEG cohort. Approximately 900 PD subjects and 800 controls have enrolled in both cohorts.
We propose here to continue to collect measures of motor and non-motor progression on PEG2 subjects as well as biological samples. We will also determine if certain environmental (e.g. pesticides, medication, occupations etc), genetic polymorphisms (genetic variations), or epigenetic markers (environmental changes to genes that can be passed on) determine the rate of disease progression. Importantly, we will continue to share these resources (including the biologic samples) with other investigators around the world to help determine why some people progress faster than others.
Relevance to Treatment of Parkinson’s Disease: There are still no treatments that slow or stop the progression of PD despite several attempts. One reason for this is that we still do not know what determines the rate of progression in PD. Information from our studies will also be important in running a clinical trial on progression since it will help decrease the variability in the study population.
Expected Outcome: We anticipate that there will be several environmental and genetic factors that determine the rate of progression. These likely will include certain pesticides and genetic factors that alter alpha-synuclein metabolism.
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