The corn rows are high and tassled, pumpkins are gaining girth and, amid these signs the fall harvest is near, evidence is growing that farmers and others who live or work around pesticides are at greater risk for neurogenerative disorders such as Parkinson’s disease.
There is also new hope as Colorado researchers exploit genetic and other tools to find and test drugs they think have the potential to stop and even reverse the devastating neurological damage of the disease.
Parkinson’s is a progressive disorder of the nervous systems — a deficiency in a brain chemical called dopamine — that controls movement. The disease’s hallmark symptoms are tremors, stiffness and slow movements.
However, Parkinson’s effects, which can vary widely from person to person, also can include slurred speech, memory loss, depression, apathy and a slew of other debilitating symptoms. There are at least 17,000 diagnosed patients in Colorado — and a little more than 1 million in America. Hot spots are in the Midwest and Northeast.
A new examination of the incidence of Parkinson’s disease in Colorado shows a strong correlation between levels of a common pesticide, atrazine, in groundwater and the number of Parkinson’s cases here — a slightly lower incidence than the national average.
Epidemiologist Katherine James, an assistant professor at the University of Colorado School of Medicine, is preparing to publish results of an ecological study looking at a large population, 330,000 Medicare patients in 2007, with ZIP codes across the state, matched up with their potential exposure to atrazine.
Atrazine is one of the most widely used agricultural pesticides in the U.S., applied before and after planting, primarily on corn, sorghum, sugar cane and even lawns, according to the EPA. James said levels of atrazine in state groundwater haven’t changed significantly in 20 years. The CU researchers used well-water data from the U.S. Geological Survey and other publicly available records.
The group’s findings are that for every 0.01 milligram of atrazine per liter of water, there is a 4 percent increase in the risk for Parkinson’s disease. In agricultural areas, such as parts of the plains, where concentrations of the herbicide can be as high as 0.1 mg/l, there was a 40 percent increase in Parkinson’s disease.
“We are seeing that more people with Parkinson’s disease reside in areas with higher levels of herbicides in groundwater,” James said. “It’s not a causation study. We still don’t have an understanding of causality.”
A suspected cause of the disease is the accumulation in the brain of abnormal proteins, although it isn’t understood why they accumulate.
CU School of Medicine professor Curt Freed, head of the pharmacology and toxicology division, is investigating phenylbutyrate, a drug that, in his earlier study of mice, appeared to clear the brain of these protein clumps and stop the decline in brain function.
With a grant from the Michael J. Fox Foundation, Freed’s group is now giving the drug to people to see if it can mobilize abnormal protein from the brain into the bloodstream, where it can be eliminated, thus stopping the progression of Parkinson’s.
The new study results are expected in 2015. The next, definitive study, Freed said, would be a double-blind trial over the next few years in which 100 to 200 people with Parkinson’s will be given phenylbutyrate or a placebo drug, then followed for at least one year to see if the drug stops progression of the disease.
“What we’re interested in doing is stopping the underlying causes of the disease,” Freed said. “It’s a wonderful time to be doing research with all the new genetic tools available.”
These tools help researchers identify which genes are responsible for producing and modifying proteins and cell functions because it’s known that both genetic and environmental factors play roles in Parkinson’s.
More funds neededRon Tjalkens, a professor of toxicology and neuroscience at Colorado State University, is taking a different approach.
“The next sort of brass ring in the field is to slow the disease down,” Tjalkens said. “The overarching question in my lab is why do these nerve cells (that produce dopamine) continue to die.”
But rather than looking at the dopamine-producing neurons, which are generally defined as the electrically excitable cells that transmit information to the body through electrical and chemical signals, Tjalkens is studying glial cells. They function as physical support for neurons.
In trying to protect the neurons from stress or injury, however, glial cells can become overactivated and so inflamed they worsen the situation for neurons, Tjalkens said.
He and a research partner, with funding from the Fox Foundation, have patented small molecules, derived from vegetables such as broccoli and cauliflower, but then modified. They activate proteins in the cell nucleus that turn off the inflammatory response — at least in mice.
“At least in animals we’re able to freeze the diseases with just a single daily dose of these small molecules,” Tjalkens said. “It’s looking really promising. The difficulty is raising money.”
Until research produces conclusive results, Coloradans can reduce their exposure to these chemicals.
A pesticide link to Parkinson’s has been suspected since disease clusters showed up in Vietnam veterans who had been exposed to herbicides such as Agent Orange.
Pesticides gained more researcher attention in the early 1980s after an outlaw chemist in northern California, attempting to produce a synthetic heroin, caused severe Parkinson-like symptoms in his customers. His product, according to Scientific American magazine, contained a compound called MPTP that was very similar to an ingredient in a herbicide called paraquat.
