Profile: Seeking the cause of Parkinson's

By STEVE MITCHELL, UPI Medical Correspondent  |  Dec. 14, 2002 at 3:00 PM
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Although the cause of the mental disorder Parkinson's disease remains unknown, there are some indications pesticides and other environmental chemicals might play a role in its development -- an idea that originated some 20 years ago due to an observation in heroin addicts made by Dr. J. William Langston.

Langston, who serves as science director of the Parkinson's Institute in Sunnyvale, Calif., is credited with being the first to link environmental chemicals with Parkinson's and was recently named head of a $20-million effort by the National Institutes of Health to take a closer look at the role these chemicals might play in the disease.

In 1982, a designer drug called China White, which essentially was synthetic heroin, was being manufactured illegally. It sold well until a bad batch was made. The addicts who took the bad batch immediately developed Parkinson's like symptoms. "The addicts called it 'the walking death,'" Langston told United Press International. The afflicted could not talk and lacked facial expression and most voluntary movement.

Surprising, but the addicts "responded dramatically to levidopa," a drug used to treat Parkinson's, Langston said. He eventually figured out the culprit causing the Parkinson's symptoms was a chemical called MPTP, which was found in the bad batch of China White.

This provided the first animal model for Parkinson's, he said. By treating animals with MPTP, researchers could induce Parkinson's symptoms and the animals then could be used to test whether new drugs were effective against the disease.

This also led to the hypothesis that other chemicals could cause Parkinson's.

"It provoked a huge amount of interest that other chemicals could cause the disease," Langston said. "It was a true renaissance for research in looking for environmental causes of the disease," he said. "It was a shot in the arm for Parkinson's in general. It opened the doors for the testing of new drugs and research into environmental causes."

Studies looking for environmental causes of Parkinson's found that farming, rural living, and well-water consumption early in life increased the risk for developing the disease. That finding was provocative because all of these factors could be surrogates for pesticide exposure, Langston said.

Then it was discovered the body converted the China White contaminant MPTP to MPP+, a toxin that is "strikingly similar" to an herbicide called paraquot, he said. "That got people thinking about pesticides and herbicides." MPP+ blocks the action of the mitochondria, the tiny organelles within cells that maintain separate DNA and are called the body's powerhouses.

"Recently, one study suggested that household pesticides may increase the risk of Parkinson's" but it was a small increase, he said. "To date, there's no smoking gun."

That is where the National Institutes of Health comes in. The NIH's National Institute of Environmental Health Sciences recently doled out $20 million to fund research to identify the culprit chemicals. The decision to establish a project to look at environmental chemicals and their causal role "is really quite novel because the institute is saying there's now enough evidence to try to apply a focused approach to solving this disease," Langston said.

The leading chemicals most suspected of playing a role in causing the disease include pesticides, herbicides and metals such as iron, manganese and copper, he said.

One suspected pesticide is Rotenon, the chemical of choice for organic farmers because it is derived from naturally occurring compounds in the roots of legumes and other plants. It is found in 2000 other pesticides.

A recent study found if rotenon is given to rats "they develop changes in the brain that look very similar to Parkinson's," Langston said. "Dopamine (a brain chemical) levels go down and they get ... deposits called Lewy bodies, in their brain," he said. However, the authors of the study concluded they could not say definitively whether rotenone caused Parkinson's.

Paraquot has been found to cause similar symptoms in mice.

A lot of studies currently ongoing are looking at people who apply pesticides to see if these individuals are at higher risk for developing Parkinson's.

Some scientists have not accepted the hypothesis that environmental chemicals play a major role in causing Parkinson's and instead still think there might be a genetic component to the disease. But Langston said he is convinced there is an environmental component and cites a study conducted in twins that supports his view.

Researchers examined 20,000 sets of identical twins and found in those over age 50 who had developed Parkinson's, there was "very little evidence" of a genetic link and instead suggested "something in the environment is triggering the disease," he said.

Langston's hope is the NIH-funded project will lead to the discovery the cause of the disease.

"I really do think that we will figure out the cause of the disease," he said. "We've got a lot of the pieces of the puzzle. There is a sense with a highly focused and intensive effort ... in the next five years we may get a major breakthrough regarding the cause."

Identifying the cause would help tremendously, he said. "Once you get the cause, there are two outcomes: You can actually prevent people from contracting the disease in the first place (or) you could also come up with agents that might prevent it."

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