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Unraveling Parkinson’s disease

Tuesday December 27, 2005

Marla Cone

December 25, 2005(Los Angeles Times) - A thousand acres stretched before him as Gary Rieke walked briskly behind a harvester, the parched, yellow stalks of rice sweeping against his knees. Stopping to adjust a bolt on the machine, Rieke struggled to maneuver a wrench with his trembling fingers.

Unbeknownst to Rieke, by the time he noticed the slightest tremor, some 400,000 of his brain cells had been wiped out. Like an estimated other 1 million Americans, most over 55, he had Parkinson’s disease, and his thoughts could no longer control his movements. In time, he would struggle to walk and talk.

Rieke, who was exposed to weed killers and other toxic compounds all his life, has long suspected that they were somehow responsible for his disease.

Now many specialists are increasingly confident that Rieke’s hunch is correct. Scientists have amassed a growing body of evidence that long-term exposure to toxic compounds, particularly pesticides, can destroy neurons and trigger Parkinson’s in some people.

So far, they have implicated several pesticides that cause Parkinson’s symptoms in animals. But hundreds of agricultural and industrial chemicals probably play a role, they believe.

Researchers don’t use the word ’’cause" when linking environmental exposures to a disease. Instead, epidemiologists look for clusters and patterns in people, and neurobiologists test theories in animals.

If their findings are repeatedly consistent, that is as close to proving cause and effect as they get.

Now, with Parkinson’s, this medical detective work has edged closer to proving the case than with almost any other human ailment.

In most patients, scientists say, Parkinson’s is a disease with environmental origins.

For almost two centuries, since English physician James Parkinson described a ’’shaking palsy" in 1817, doctors have been baffled by the condition.

In most people, a blackened, bean-size sliver at the base of the brain -- called the substantia nigra -- is crammed with more than half a million neurons that produce dopamine, a messenger that controls the body’s movements.

But in Parkinson’s patients, more than two-thirds of those neurons have died.

After decades of work, researchers are still struggling with many unanswered questions, such as which chemicals may kill dopamine neurons, who is vulnerable, and how much exposure is risky.

Expressed in legal terms, pesticides are not guilty beyond a reasonable doubt -- but there is a substantial, and rapidly growing, body of evidence, many scientists say.

Scientists caught the trail of pesticides in 1982, when neurologist Dr. Bill Langston treated a man who had a virtually overnight onset of Parkinson’s symptoms.Continued...

He and fellow doctors found the source to be a botched batch of synthetic heroin that contained MPTP, a compound that targeted the same neurons missing in Parkinson’s patients.

Paraquat has been one of the world’s most popular weed killers for decades.

Since that discovery, scientists have conducted hundreds of animal experiments, at least 40 studies of human patients, and three of human brain tissue.

They have found ’’a relatively consistent relationship between pesticide exposure and Parkinson’s," British researchers reported online in September in the journal Environmental Health Perspectives.

To pinpoint which environmental exposures are most important, scientists are trying to unravel how genes and toxic chemicals interact to destroy brain cells.

One leading theory is that pesticides cause over-expression of a gene that floods the brain with a neuron-killing protein.

Exposure to chemicals early in life, followed by toxic exposures in adulthood, may be especially important, triggering a slow death of neurons that debilitates people decades later.

Compounds with little in common, such as a fungicide and an insecticide, apparently can team up to decimate brain cells.

More than 1 billion pounds of herbicides, insecticides, and other pest-killing chemicals are used on US farms and gardens and in households. Nearly all adults and children tested have traces of multiple pesticides in their bodies.

So far, animal tests have implicated the pesticides paraquat, rotenone, dieldrin, and maneb -- alone or in combination -- as well as industrial compounds called PCBs, or polychlorinated biphenyls.

Still, the science of epidemiology has inherent weaknesses. Most of the human studies, for example, relied on patients’ memories -- most of which cannot be validated -- to report their pesticide exposures.

’’You need to be cautious in drawing conclusions when you know there are flaws in these studies," said Pamela Mink, an epidemiologist who evaluated the human studies in a peer-reviewed report partly funded by the pesticide industry.

Most patients probably were exposed decades before their diagnosis.

Because there is no national registry for Parkinson’s, as there is for cancer, no one knows whether rates are high in places such as the San Joaquin Valley.

Among those trying to obtain more definitive answers, UCLA environmental epidemiologist Dr. Beate Ritz has contacted nearly 300 Parkinson’s patients and 250 healthy people in California’s Tulare, Fresno, and Kern counties.

She is pinpointing their pesticide exposures down to the day, the pound and the street corner by overlaying their addresses with California’s extensive agricultural database, which details pesticide use on farms since the 1970s.

Also, 52,000 farmers and other pesticiding evidence yet on how everyday environmental factors can play a role in Parkinson’s disease. Her theory was that testing one chemical at a time for its impact on the brain was misguided.

Paraquat and maneb are unlikely to be the only combination with such a devastating effect. Yet the US Environmental Protection Agency considers only single exposures when approving pesticides, an approach that ’’doesn’t mimic environmental reality," Cory-Slechta said.

For Rieke, it is impossible to determine which chemicals may have played a role in his disease. He owned two dry-cleaners -- handling industrial solvents for seven years -- and for 25 years he mixed and applied at least a dozen herbicides and insecticides on his Merced farm.