Three former co-workers of Michael J. Fox all have Parkinson's disease, causing speculation that the disease may have an environmental cause. Nobody knows what causes Parkinson's disease. Scientists look for disease clusters, hoping this will help them turn up clues that can help with the search for a cure.
Fox and the three other people with Parkinson's disease were among 125 people who in the late 1970s worked on a Canadian television show called Leo & Me. Four cases among 125 people -- especially young people -- is highly suspicious. Each year Parkinson's strikes only about 1 in 10,000 people, nearly always much older people than the sitcom cast and crew.
Fox is being treated in the U.S. His three co-workers are being treated by Dr. Donald B. Calne, director of the neurodegenerative disorders center at the University of British Columbia in Vancouver. Calne says the odds of this happening by chance are as little as 1 in 20,000. "We do have a group of Parkinson's disease cases that seems to be more than coincidental," Calne says. "These people worked together here in Vancouver from 1976 to 1980. We want to find as many other crew and cast members as we can and see how their health is. We'll be looking at the building they worked in to see if we can find any clues."
Dr. J. William Langston, founder and president of the Parkinson's Institute in Sunnyvale, California, says he thinks the Fox cluster is real. "Four cases in a small group in a short period is very unlikely to be chance -- particularly because they were young-onset cases," he says. "That is what really puts it into statistical orbit. The younger cases are extraordinarily rare."
Langston says Fox told him about the cluster of cases some years ago, but it didn't become public knowledge until recently, when it became part of a soon-to-be-aired Canadian documentary. The program suggests that this cluster may offer a clue to the cause of Parkinson's disease. Calne and Langston think so, too -- and they've begun hearing about other, similar Parkinson's clusters.
"As a result of all the media attention, we are getting very interesting reports of other Parkinson?s disease clusters," Calne says. "We are interested in hearing of more. Right now we are planning a strategy to try and prioritize investigation of the various clusters we have heard about because of this publicity. We feel it is important."
The most recent Parkinson's cluster occurred in the early 1980s, when cases of began appearing among young people in San Francisco. Langston showed that these cases were caused by a chemical contaminating synthetic heroin. Another clue comes from the 1917 worldwide epidemic of von Economo encephalitis. Years after recovering from this disease -- thought to be caused by a now-extinct virus -- many patients developed Parkinson's disease, showing that infections can leave a person vulnerable to Parkinson's.
Calne suspects something similar happened to Fox and his co-workers. "We think there was probably quite a brief exposure some years before symptoms occurred," Calne says. "The way we see it is that probably some quite common virus infects someone and -- because of a particular state of susceptibility at that time -- it gets into the brain. Maybe this is because they had another infection or a toxic exposure. But they are not infective at all -- you can't catch Parkinson's disease from a person who has it."
A cluster of cases occurred among members of the physics department at the University of Pittsburgh when, over a 10-year period, four professors were diagnosed with Parkinson's disease. Neurologist Michael J. Zigmond, PhD, led the investigation. "There's a couple of serious problems in trying to understand these clusters," Zigmond says. "The first is, we don't know what causes Parkinson's. You can measure whatever you like, but we don't know what to look for. We didn't find anything on the short list of compounds people already feel there is reason to be concerned about. The second problem -- and this is the case for the Fox cluster, too -- is that there is a long delay between the time the disease begins and the time it shows up as a clinical problem. Whatever happened could have taken place on a single day over a period of years. We just don't know enough."
Parkinson's disease affects a very specific set of brain cells and symptoms of the disease only occur when about 80% of these cells die off. "If you think of a battle, these nerve cells are like soldiers," Calne says. "The event that causes Parkinson's is like a battle. Some cells are killed outright, some are unscathed, and some are wounded so that they die prematurely. It is that premature death that leads to Parkinson's disease."
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A Parkinson's patient has been treated with a transplant of his own brain cells. The treatment cleared up the trembling and rigid muscles that mark the disease. The patient, a nuclear engineer and jet pilot, developed Parkinson?s in his 40s. More than two years after the experimental treatment, he has no symptoms of Parkinson's.
The researchers isolated and nurtured adult stem cells from the patient?s brain, then re-injected them to restore normal function. "We definitely need to do more studies," says Dr. Michel Levesque of the Cedars-Sinai Medical Center in Los Angeles, who led the study. "This is the first case that shows a promising technique may work. It is an experimental procedure and has to be investigated further before it becomes accepted procedure."
Many different groups of researchers are experimenting to see if brain cells damaged by Parkinson's can be regenerated using stem cells, the master cells that give rise to the various different tissues in the body. Stem cells can come from very early embryos, or can be found in a person's own tissues, although these are sometimes hard to obtain.
Levesque's team drilled into the patient?s skull and removed a piece of his brain. "We took a tiny piece of cortex measuring probably less than the size of a pea," Levesque says. "What we extracted were neural stem cells or progenitor cells."
It?s hard to tell whether a cell is a stem cell, but they grew the cells in special media, a kind of nurturing soup. They checked to make sure at least some of the cells were producing dopamine, the substance needed by Parkinson?s patients, then injected them back into the patient?s brain. PET scans of the man?s brain, which show brain function, revealed that dopamine was being produced and used. "At three months there was a 58 percent increase," Levesque says.
The most puzzling finding is this: the man's dopamine production, as measured by PET scans, is back to where it was when he was first treated, yet the symptoms of Parkinson's have not returned.
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