BY Christina Elston
LOS ANGELES May 05: Cedars-Sinai Health Sciences University investigators are bringing their stem cell expertise to a collaboration with two other academic medical centers with the goal of clarifying the connection between pesticide exposure and Parkinson’s disease.
The project, which includes investigators from UCLA, the University of Southern California (USC), and the University of Münster in Germany, is funded by a three-year, $9 million grant from Aligning Science Across Parkinson’s, in partnership with The Michael J. Fox Foundation for Parkinson’s Research.
In the debilitating neurodegenerative condition, one of the major problems is that brain cells producing dopamine—the chemical in the brain that helps nerves coordinate muscle movement—die more rapidly than normal. As these cells die off, patients experience tremor, stiffness, and movement and balance issues.
“We think that Parkinson’s disease is caused by a combination of genetic traits in the patient and environmental exposures—especially to certain pesticides and air pollution,” said Clive Svendsen, PhD, executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute and one of the principal investigators of the study. “It seems the genes load the gun while the environment pulls the trigger. With this grant, we will generate lines of stem cells from people living in a pesticide-treated area in the San Fernando Valley and attempt to figure out why some developed Parkinson’s and some did not.”
Svendsen said that only about 5%-10% of Parkinson’s disease cases are caused by a single genetic mutation, and evidence is building that mutations in many other areas of the genome may also contribute to disease.
“If you have mutations in an array of different genes, we know that increases your risk for developing Parkinson’s,” Svendsen said. “We are trying to determine which of those genetic vulnerabilities interact with pesticides—and how. If we can figure that out, we can begin to think about new approaches to treatment.”
The team will recruit groups of relatives—some who developed Parkinson’s disease and some who did not. Investigators will reprogram participants’ cells to create induced pluripotent stem cells, which they can then turn into dopamine-producing neurons that replicate the brain cells at risk in Parkinson’s patients. They will then expose those cells to the pesticides or air pollution present where the participants live.
“By investigating how the environment and a person’s unique genetics interact to drive Parkinson’s, this team is uncovering the diverse biological drivers of the disease,” said Sonya Dumanis, PhD, managing director of ASAP. “This is exactly the kind of bold, integrative science the Collaborative Research Network is designed to accelerate. With a better understanding of these disease mechanisms, we can lay the groundwork for new, personalized therapeutics and better outcomes for Parkinson's patients."
The investigators’ theory is that the dopamine neurons generated from people with Parkinson’s disease will die more quickly after pesticide exposure than the neurons from family members exposed to the same pesticides or air pollution who did not develop the disease.
“If that turns out to be the case, we can compare the genetic makeup of those individuals, and the proteins their genes express, and try to figure out what triggered the development of Parkinson’s disease in some of them but not others,” Svendsen said.
