MAIN CAUSE OF PARKINSON

DISEASE: Genes trigger only a small number of cases, study find. Pesticides are sited as possible culprit.

Article from the Los Angeles Times, Wednesday January 27, 1999

By Thomas H. Maugh II
Times Medical Writer

A defective gene does not cause most cases of Parkinson's disease, but rather by exposure to as yet unknown chemicals in the environment, California scientists reported today.

The discovery should provide some comfort to family members of Parkinson's victims who fear for their own future health, said the research team from the Parkinson's Institute in Sunnyvale. The study also suggests that research should focus on potential environmental causes, such as pesticides and herbicides, they added.

Genetics is a factor, however, in the relatively small number of patients-less than 10%, whose familial Parkinson's begins under the age of 50. A gene that has been identified causes their disease.

Based on previous studies with small numbers of twins, scientists have long suspected that genetics did not play an important role in the disease, which affects more than a million Americans. The new study of nearly 20,000 white male twins who ought in World War II seems to confirm that definitively.

Dr. Caroline M. Tanner and her colleagues at the Parkinson’s Institute report in today’s Journal of the American Medical Association that the disorder most commonly affected only one member of a twin pair, whether the pair consisted of identical or fraternal twins.

If the disease were genetic in origin, both members of a pair of identical twins-who share all their genes-would be expected to develop it.

This “landmark study...provides guidance that is extremely important”, said Dr. Michael D. Walker of the National Institute of Neurological Diseases and Stroke. “For patients over the age of 50, it means that we are going to have to look elsewhere for causes.”

But the study of the younger patients with a familial form of the disease will remain important, said Dr. Neat Hermanowicz, medical director of the movement disorders program at Hermanowicz, medical director of the movement disorders program at Good Samaritan in Los Angeles. “Any time you have a gene for a disease, whether it applies to all cases or not, it gives you a huge leg up in understanding the disease process.”

Parkinson’s disease results from the death of certain brain cells that secrete dopamine, a chemical messenger used for controlling movements. The major symptoms include tremor, stiffness of muscles and bradykinesia, or slowness of movement.

It is commonly treated with drugs that replace the lost dopamine. Transplants of fetal tissue that secrete dopamine have also been helpful. Tremors can sometimes be controlled by pallidotomies*, which in a small section of the brain is destroyed, or by implanting electrodes. But there is no cure and the disease is usually fatal.

An estimated 60,000 people develop Parkinson's each year, and that number is expected to climb as the population grows older.

The idea that Parkinson's might be caused by chemicals in the environment got a major boost in 1982 when Dr. J. William Langston, now president of the Institute and a co-author of the current paper, discovered several young people who developed Parkinson's symptoms literally overnight after using tainted heroin. He found that the symptoms were caused by a contaminant called MPTP, which bears a strong chemical similarity to many pesticides and other environmental chemicals.

Two years ago, researchers also discovered that the disease could be caused, at lease in some Italian and Greek families, by defects in the gene for a protein called alpha-synuclein.

Many authorities that had supported an environmental cause flip-flopped; back to favoring a genetic origin, Hermanowicz said.

To clear up the confusion, Tanner and her colleagues studied 19,842 surviving white male twins who are enrolled in the National Academy of Sciences/National Research Council World War II Veterans twin Registry.

They identified 193 individuals who had a confirmed case of Parkinson's disease. Among those who developed the disorder after age 50, the likelihood that their twin brother would also have Parkinson's was no greater than the risk for the population at large, whether the twin was identical or fraternal.

Such results normally mean that there is little or no genetic contribution to the disease.

For the first time, we can say that typical Parkinson's disease is most commonly caused by environmental factors, Tanner said.

Among the 16 twins who were under 50 when they developed the disorder, however, there was a high likelihood that the second identical twin would contract it, and a lower, but still elevated, risk that a fraternal twin would. The finding indicated that for these families the disorder is genetic in origin.
The team has collected a great deal of information about environmental exposures among the twins, Tanner added, and will begin plowing through the data in hopes of narrowing down the number of potential causes.

*Destruction of the glubus pallidus done to treat involuntary movements or muscular rigidity.

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