Very important article in NY Times today

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May 14, 2002

Parkinson's `Clusters' Getting a Closer Look

By MARY DUENWALD

ichael J. Fox's celebrity can do more than raise money for Parkinson's research. It may also help open an avenue of research that scientists have long wanted to explore.

Mr. Fox, it turns out, was one of four people who worked on a production crew at a television studio in Vancouver, British Columbia, in the late 1970's and developed Parkinson's disease. Given that only 125 people worked on the crew in those years — including actors, directors, writers, production people and technicians — the number of cases seems extraordinary.

It is possible that the cluster of cases arose purely from chance. But researchers are interested in studying them in hopes they will lead to clues to possible environmental factors or even viruses that may contribute to to the disease.

Typically, Parkinson's disease afflicts one in 300 people. In people as young as J. Fox, 30 when the disease was diagnosed in 1991, the illness is much rarer. Fewer than 5 percent of Parkinson's patients develop symptoms before age 50, said Dr. Caroline Tanner of the Parkinson's Institute. The Vancouver cluster includes Mr. Fox and a woman who learned she had Parkinson's at age 38.

The four people worked together from 1976 to 1980, when it is possible that the disease began in all of them. Parkinson's progresses gradually, taking 5 to 10 years from the time it starts to the appearance of the first symptoms — usually, rigidity in an arm or leg or tremor in a hand.

Dr. Calne, director of the neurodegenerative disorders center at the University of British Columbia, estimates that the odds of the four cases occurring at the same time in such a small group of people are less than 1 in 1,000.

He and other scientists say the cluster warrants investigation.

"I would definitely want to look further," said Dr. J. Langston, director of the Parkinson's Institute in Sunnyvale, Calif., and chief scientific adviser to the J. Fox Foundation for Parkinson's Research.

Dr. Katrina Gwinn-Hardy, a Parkinson's specialist at the National Institute of Neurological Disorders and Stroke, said, "It's intriguing and worth pursuing."

Mr. Fox said he was curious about the cluster, out of both empathy for the people he worked with and because, as he put it, "the beginning of my career and the end of my career being tied in a single event is pretty cosmic or weird to me."

But whether the cluster should be investigated, he said, is a question he leaves to the judgment of scientists.

Clusters of Parkinson's cases occur from time to time, when, for example, a number of people in a neighborhood or small town develop the disease. But they often go unnoticed or are ignored because scientists lack the time and money to look into them. In this case, the publicity surrounding Mr. Fox's admission that he had Parkinson's, nearly three and half years ago, drew the cases into the spotlight.

Don S. , who directed Mr. Fox in two Canadian situation comedies beginning when the actor was 16, and who also has Parkinson's, tried to get in touch with Mr. Fox soon after reading the news. "But I couldn't get past his handlers," he said.

Mr. (also a cast member of "The X Files" for four years) learned of his illness nine years ago, when he was 55.

Sally Gardner, whose Parkinson's was diagnosed when she was 38, in 1984, had been a script supervisor in the late 1970's, and had worked with Mr. Fox and Mr. . The fourth member of the cluster, a cameraman who has kept his identity secret, was recently found by Jerry , writer and director of a Canadian television documentary about Mr. Fox and Parkinson's disease. The cameraman's diagnosis came at age 54.

's documentary, "The Parkinson's Enigma," which was broadcast last month, publicized the cluster's existence.

Could something at the television studio have caused the disease in all four people? Dr. Calne, Dr. Langston and other experts believe it could have. Perhaps something they breathed or ate or drank — a toxin, perhaps, or an infectious agent — set the disease process in motion.

"If this is a genuine cluster and not a statistical fluke," said Dr. Oliver Sacks, a neurologist and writer, "it would certainly suggest an environmental agent at work."

The mystery is especially compelling because scientists do not know what causes most cases of Parkinson's. Most believe that both genetic and environmental factors are at work. "We often say that maybe people have some gene that predisposes them to be susceptible to any number of things in the environment," said Dr. J. Weiner, chairman of neurology department at the University of land School of Medicine. "But's that's probably just another way of saying we don't know the cause."

The disease occurs when cells in the substantia nigra, a darkly pigmented part of the midbrain, about half the size of an adult index fingernail, start to die off. These cells produce dopamine, a chemical messenger that is essential for normal muscle movement. The cell death occurs gradually, and that is why Parkinson's can go unnoticed so long.

Once dopamine production declines by about 80 percent, the patient begins to experience the four classic symptoms: tremor, stiffness, slow movement and problems with walking, posture and balance. In some cases, the cell death is set off by genetic mutations. Scientists have identified two genes that are involved in Parkinson's disease and have pinpointed the locations of four others.

But Parkinson's does not seem to be primarily a genetic disorder. It runs in the families of only about 10 percent to 15 percent of patients, Dr. Tanner of the Parkinson's Institute said. A large study she conducted indicated that the identical twins of Parkinson's patients are no more likely to have the disease than fraternal twins — a sign that the disease is not largely genetic.

Environmental agents have also been known to create Parkinson's symptoms. In the era of World War I, for example, some people who had contracted the virus that causes sleeping sickness later developed what came to be known as post-encephalitic parkinsonism, a particularly severe disorder that left people in trancelike states. Dr. Sacks's book "Awakenings" told how these patients were able to regain movement when he treated them with levodopa, a drug that is still the main treatment in Parkinson's. (Levodopa, also known as L-dopa, is converted to dopamine in the brain.)

It is possible that a virus could also have been involved in the so-called Fox cluster. "It is important to look for infectious as well as toxic agents," Dr. Sacks said.

Dr. Calne suspects a virus may indeed have caused the Parkinson's cases in Vancouver. "In many areas of medicine it is fully accepted that there are several types of cause for one type of disorder," he said. "For example, everyone recognized that cancer can be caused by genes, chemical agents or infective agents. In the field of neurodegeneration, people are often reluctant to draw the same general conclusion, in spite of compelling evidence."

Perhaps, Dr. Calne said, Parkinson's can be caused by a single event, when an infection or a toxic substance attacks cells in the substantia nigra. Some cells are killed instantly; others are injured and die off over time, causing the patient's symptoms to worsen progressively.

The idea that viruses can cause Parkinson's, he said, is bolstered by evidence that the disease has been somewhat more prevalent among people who have worked in certain fields, including teachers, doctors, dentists, nurses, loggers and miners. These people all had relatively high exposure to infections — teachers and doctors because of the people they worked with and loggers and miners because they slept in close quarters in work camps.

Mr. does not recall any particular illness he suffered while working on the television production crew. "You know what it's like with flu and colds and things; they're not outstanding events," he said.

Toxins can also set off parkinsonism, as doctors learned in 1983, when seven young adults in the San Francisco Bay Area suddenly developed symptoms. Dr. Langston examined this cluster of patients and learned that they all had injected themselves with a synthetic form of heroin that contained the toxic molecule MPTP. The MPTP killed large numbers of the victims' dopamine-producing cells.

Dr. Calne has already been in touch with the production studio about starting an investigation in the cluster. "I'm not optimistic about finding a cause after all this time," he said, "but I think we might be able to find some features of the circumstances that might be helpful. I think we'd be derelict in our responsibility if we ignored this."

Already, Dr. Calne believes he may have one intriguing clue. The production studio, a largely underground structure in downtown Vancouver, is heavily insulated because of the need to block out sound.

"Obviously the air circulation is very tight," Dr. Calne said. "And so if there was anything in the environment, there may have been a bigger risk of that being recirculated to an extent that might amplify risk."

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