Pesticide exposure may increase Parkinson’s risk for those with genetic mutation

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Published November 27, 2013

| FoxNews.com

People with a genetic mutation linked to Parkinson’s disease may have an increased risk of contracting the neurodegenerative disorder if they have been exposed to certain pesticides, according to a new study published in the journal Cell.

Conducted at the Massachusetts Institute of Technology and the Sanford-Burnham Medical Research Institute in La Jolla, Calif., the research involved using human stem cells, derived from a patient with Parkinson’s disease, to analyze the relationship between Parkinson’s and pesticides.

Though previous epidemiological and animal studies have attempted to prove a connection between exposure to pesticides and a higher susceptibility to Parkinson’s, this was the first study that successfully used human cells to examine the link.

To conduct their analysis, researchers gathered skin cells from a Parkinson’s patient who possessed a genetic mutation linked to the disease, in the gene encoding a protein called alpha-synuclein. The researchers then transformed these skin cells into human induced pluripotent stem cells (hiPSCs) and “corrected” the Parkinson’s mutation in half of the cells, in order to provide a basis for comparison. 

Researchers then transformed all of these hiPSCs into a specific type of nerve cell damaged in Parkinson’s disease: A9 dopamine-containing neurons. These nerve cells are the first to be affected by Parkinson’s disease and are linked to motor sequencing, or the ability to start and stop movements – a common problem in Parkinson’s patients.

“Many think of Parkinson’s disease as tremor, shaking, rigidity and stiffness. But it’s also very important to know that it is the sequencing of movements – beginning and stopping a movement – where patients really get into trouble… and these particular cells really control that,” lead study author Dr. Stuart Lipton, professor and director of Sanford-Burnham Medical Research Institute's Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, told FoxNews.com.

Researchers then exposed the nerve cells to a combination of pesticides, including paraquat, maneb, and rotenone, which are commonly used in agricultural settings in the United States. Notably, the levels of exposure tested by the researchers were well below EPA-recommended levels.

“We did a dose response of pesticides, and that particular dose had been implicated in the human epidemiological studies as being strongly associated with Parkinson’s,” Lipton said. “And what we found is we could give very low doses of that combination (of pesticides), and the cells with the genetic mutation would die – and the cells without that would not.”

Overall, the researchers determined that exposure to pesticides seems to increase the likelihood that people with a genetic risk for the disease will actually go on to contract the illness.

“If you’re susceptible to Parkinson’s disease, you will be more susceptible to getting it earlier if you are exposed to pesticides,” Lipton said.

Approximately 50,000 Americans are diagnosed with Parkinson’s disease every year, and the Centers for Disease Control and Prevention recently named the illness as the 14th leading cause of death in the United States. Lipton and his colleagues hope their research will help pave the way for more studies into new treatment or prevention methods for Parkinson’s disease in the future.

“You should be able to screen people and tell them if they have a repertoire of genes. Then they might want to avoid exposures to pesticide,” Lipton said. “Another option is to take these susceptible cells and then…screen for drugs known and not-yet known that can protect these cells. And we already have several compounds of interest.”

Furthermore, Lipton and his colleagues believe their research will shed light on how certain genetic and environmental factors interact to make people more vulnerable to a wide array of neurodegenerative diseases.  Lipton said this could help pinpoint the “cause” of these diseases in certain individuals.

“This raises an important question for all neurodegenerative diseases of how much is it the genes, how much is it the environment and how much is both and the interaction between them?” Lipton said. “I think that’s important for every neurodegenerative disease.  You have a set of genes that makes you susceptible, but then there’s a second hit, something in the environment, which predisposes you to the disease.”

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