A new study from researchers in the Khurana lab at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, in close collaboration with researchers from the Ritz lab at UCLA and the Rubin lab at Harvard University, identified pesticides that could be relevant to the development of Parkinson’s disease. The study was led by Richard Krolewski, MD, PhD, a neurologist in the Brigham’s Division of Movement Disorders and Ann Romney Center for Neurologic Diseases, and Kimberly Paul, PhD, from UCLA, along with collaboration with Edinson Lucumi Moreno within the Khurana lab at the Brigham.
Both genetic and environmental factors may influence the likelihood of developing Parkinson’s disease. Using agricultural records, the researchers investigated 288 pesticides, finding that long-term exposure to 53 of these pesticides was associated with Parkinson’s disease. The team then used a screening system in dopamine neurons derived from Parkinson’s patients to study 39 of those pesticides and identified 10 that were directly toxic to dopamine neurons. The study also found exposure to multiple pesticides used in combination, such as in cotton farming, is more toxic to dopamine neurons than any single pesticide.
“The combination of bench science and epidemiology is quite novel here,” said Krolewski. “The bench science is able to address questions that are difficult to answer with epidemiology while the epidemiology helps direct the bench science – the sum is greater than the parts.”
The Department of Defense supported this project and has now supported the group to utilize diverse stem-cell models derived from Parkinson’s patients to investigate how pesticides and the gut microbiome disrupt key neuronal processes affecting both movement and cognition.
“The findings advance a major goal of the BWH Movement Division to tailor therapies to specific triggers of Parkinson’s in each patient,” said Khurana.
Read more in Nature Communications.
Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Cells
Article Title
A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides
Article Publication Date
16-May-2023
COI Statement
L.L.R. is a founder of and a member of the Scientific Advisory Board of Vesalius Therapeutics, a private biotechnology company, and an owner of stock options. He is a member of the Scientific Advisory Board of Yumanity Therapeutics and a shareholder. Both companies study Parkinson’s disease. B.R., M.C., and R.C.K. have been retained as expert consultants for plaintiffs in a lawsuit on the role of paraquat in Parkinson’s disease causation. V.K. is a co-founder of and senior advisor to DaCapo Brainscience and Yumanity Therapeutics, companies focused on central nervous system diseases. The remaining authors declare no competing interests.