UCLA Health will lead a $9 million, multi-institution research project to further elucidate the link between exposure to pollutants including certain pesticides, air pollution and the increased risk of Parkinson’s disease.
The three-year research project is being funded by Aligning Science Across Parkinson’s (ASAP), in partnership with The Michael J. Fox Foundation for Parkinson’s Research (MJFF), as part of an expansion of ASAP’s Collaborative Research Network (CRN). Helmed by UCLA with collaboration from researchers at Cedars-Sinai and the University of Münster in Germany, the project will analyze populations exposed to pesticides and air pollution, stem cells as well as animal models to identify the molecular pathways linking exposure to environmental toxins to the development and progression of the neurodegenerative disease.
“We have known for some time about the risks of chronic exposure to these commonly used pesticides and air pollution, but the mechanisms underlying these risks still remain unclear,” said project lead Dr. Jeff Bronstein, a movement disorder neurologist at UCLA Health and director of the Levine Family Center for Movement Disorders at UCLA. “We seek to deepen our understanding of the specific pathways impacted by exposure to these toxicants, which we hope can lead to treatments to prevent more cases of Parkinson’s disease or slow disease progression.”
Previous studies in the Central Valley led by Dr. Beate Ritz from UCLA found that people exposed to certain pesticides, such as chlorpyrifos and paraquat, and air pollutants, such as small particulate matter, had higher risk of developing Parkinson’s disease, with the risk increasing the longer they were exposed.
The current hypothesis is that the increased risk is caused by both environmental exposure and a person’s genetics, which may explain why some develop Parkinson’s disease at a faster rate. Parkinson’s disease has been linked to several genetic mutations, with researchers believing exposure to pollutants working to trigger the progression of the disease.
The new study will use advanced genetic and protein analyses of human brain cells derived from the stem cells of people in the Central Valley who have experienced varying exposure to pesticides or air pollutants. Dr Clive Svendsen, executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai, and his team of leaders in the field of stem cell biology, will derive stem cells from subjects from the Central Valley, induce them to become dopamine neurons and then expose these cells to the three toxicants and analyze how they alter their DNA, RNA and proteins.
Additionally, the research will also use animal models, including zebrafish and mice, in parallel with human cells to attempt to identify the molecular pathways that impact the rate of disease progression. The team will then work to alter the genetics of the human cells and animal models to determine whether the disease onset can be halted or slowed.
Parkinson’s disease is a neurodegenerative disease caused by the damage and death of nerve cells in the brain. This degeneration significantly reduces the brain’s production of dopamine, which is crucial for coordinating muscle movement. As a result, people living with Parkinson’s disease experience symptoms such as tremors, slow movement, freezing of gait and stiff muscles.
About 1 million people in the U.S. and 10 million people worldwide live with the disease, with diagnoses having nearly doubled in the U.S. in the past decade. There is no known cure.
The study is expected to begin in June and end in 2029.
“Understanding a disease this complex requires bringing together expertise across disciplines and institutions,” Bronstein said. “This collaboration and grant funding give us the tools and the scale to ask questions we haven't been able to answer before.”
Co-principle investigators of the study also include Drs. Beate Ritz, Chao Peng, William Zeiger, Jesus Araujo, and Kimberly Paul of UCLA, and Dr. Christina Lill of the University of Münster.
As part of a separate study supported by the ASAP and The Michael J. Fox Foundation grants, UCLA researchers will collaborate with the University of Dundee. The study will investigate how cellular stress pathways intersect with mitochondrial function to influence Parkinson’s risk.
“We seek to understand how these pathways crosstalk and compensate in the context of Parkinson's disease progression by studying mitochondrial clearance in situ in cultured dopaminergic neurons and human brain samples, paving the way for the development of new therapeutic strategies that restore mitochondrial function,” said study collaborator Rosalie Lawrence, assistant professor of biological chemistry at the David Geffen School of Medicine at UCLA.
More information about the grant funding can be found at https://parkinsonsroadmap.org/news/261m-investment-toward-personalized-treatments/
