Neurotoxin Exposure Treatment Parkinson's
Investigating the Gene-Environment Interactions Related to Parkinson’s Disease Susceptibility
Posted October 20, 2021
Samuel Goldman, M.D., M.P.H., Northern California Institute for Research and Education
Raymond Swanson, M.D., Northern California Institute for Research and Education
Parkinson’s disease (PD) is a neurodegenerative disease that progresses over time as small clusters of dopamine‐producing brain cells deteriorate, causing motor issues such as tremors, loss of coordination, and difficulty speaking. The Parkinson’s Foundation estimates that there are one million Americans currently living with PD. Although the exact cause of disease onset is unknown, it is thought that a combination of genetic and environmental factors, as well as the interaction between them, are contributors.1 In 2010, the U.S. Department of Veterans Affairs acknowledged that exposure to Agent Orange and other neurotoxins is associated with PD.2 However, there have been limited studies on the gene‐environment interactions that contribute to a PD diagnosis and none have been replicated.
Through a Neurotoxin Exposure Treatment Parkinson’s Program (NETP) Fiscal Year 2019 Investigator‐Initiated Research Award, Drs. Samuel Goldman and Raymond Swanson at the Northern California Institute for Research and Education aim to uncover the link between genetic and environmental factors as they contribute to individual risk for PD. The team will use whole‐genome sequencing and bioinformatics to investigate the genetic variants involved in susceptibility to PD. First, the investigators will use induced pluripotent stem cell (iPSC) cell lines exposed to toxins such as paraquat and permethrin to determine whether glutathione S‐transferase theta-1 (GSTT1) deletion increases susceptibility. They will also assess samples from the National Institute of Environmental Health Sciences Farming and Movement Evaluation (FAME) study database to examine other genes that contribute to increased susceptibility to pesticides and other persistent organic pollutant exposures, which will be characterized both historically and through serum analysis. Drs. Goldman and Swanson plan to use whole‐genome sequencing and novel machine learning and bioinformatics approaches for the FAME database analysis, and will also focus on Service-related neurotoxin exposures. They will use iPSC‐derived neuronal cell lines to confirm the genes that are shown to confer susceptibility and the extent to which those genes play a role in individuals of varying genetic backgrounds.
Over 300 samples from the FAME study database will be examined in this groundbreaking study with the goal of conclusively linking environmental risk factors and susceptibility to PD. If successful, this project could provide the framework for PD risk identification and prevention strategies based on combined environmental and genetic data at the individual level, which is especially important for military personnel with known neurotoxin exposures.
Public and Technical Abstracts: Integrating Environmental, Genomic, and Functional Data to Characterize Individual Risk for Parkinson’s Disease