Discovery Put Parkinson’s Research on a New Path
In 1982, neurologist J. William Langston, then at Stanford University, stumbled across a small group of men in their 20s who had unexpectedly developed the paralyzing symptoms of Parkinson’s disease, which usually strikes people over 50. He shortly discovered that the symptoms had been produced by a contaminant, called MPTP, in a synthetic heroin that the men had either been manufacturing or using.
That discovery sparked a powerful resurgence in research on Parkinson’s because it made it possible to produce the disease in animals. When injected into the brain, MPTP selectively kills cells in the substantia nigra, producing a condition virtually identical to Parkinson’s disease. This discovery provided researchers with a means to study the development of Parkinson’s and to test new forms of therapy.
Today’s announcement by Langston and James W. Tetrud that deprenyl delays progression of the disease is a direct outcome of that discovery. Furthermore, the discovery that Parkinson’s can be caused by a chemical has led many neuroscientists to the conclusion that the disease is caused by toxins in the environment, including pesticides and chemicals used in making paper.
A key development in the history of MPTP was the discovery by researchers at UC San Francisco that the chemical itself is not toxic to brain cells. Instead, an enzyme in the brain called monoamine oxidase-B (MAO-B) converts it into a metabolite called MPP+ that actually kills the cells.
Based on this observation, Langston and others began testing drugs that would inhibit the action of MAO-B, hoping to prevent the formation of MPP+. “The results were really dramatic,” Langston said. He found that giving deprenyl to the animals before injecting MPTP completely blocked the killing of brain cells. “That was the key . . . that led us to trying deprenyl in humans.”
The discovery also stimulated new research into the causes of Parkinson’s. In the past, researchers had assumed that the disease was inherited. But three large studies of identical twins, the most recent published by Finnish researchers in November, 1988, indicated that genetics plays only a small role.
The environmental link occurred to researchers because MPTP has a striking resemblance to many chemicals man has placed in the environment. Several preliminary studies have tentatively implicated such chemicals in causing the disease.
The late Andre Barbeau of the Clinical Research Institute in Montreal, for example, compared the incidence of Parkinson’s in several regions of Canada to use of pesticides and herbicides.
He found that a major agricultural region southwest of Montreal where use of the chemicals was very high had the highest incidence of Parkinson’s (0.89 cases per thousand population). In a region where pesticide use was very low, in contrast, the incidence of Parkinson’s was only 0.13 cases per thousand.
Scandinavian researchers have reported similar results among people who live near pulp and paper mills.
Most recently, neurologist Donald Calne of the University of British Columbia reported his discovery of families in which several members developed Parkinson’s about the same time. If the disease were genetic, they would have developed it about the same age. The fact that they were different ages when they developed the disease more or less simultaneously suggested that it was caused by environmental exposure.
