Parkinson’s Researchers Zero In on Gene
Federal scientists have narrowed the search for a gene that causes one form of Parkinson’s disease to a small segment of one human chromosome, providing the first direct evidence that a genetic alteration is capable of producing the devastating brain disorder.
The results offer new hope for early detection and improved treatment of the disease, which affects more than 1 million Americans, the researchers say.
The discovery, reported today in the journal Science, “gives us a powerful new tool to understand why nerve cells die in Parkinson’s disease and how to stop them from dying,” said Zach Hall, director of the National Institute of Neurological Diseases and Stroke. “It will usher in a new era of Parkinson’s disease research.”
“This is an exciting moment, but it is really only a beginning,” added Dr. Matt Kurtz of the Barrow Neurological Institute in Phoenix.
What researchers have done in the new work is akin to looking for a single individual in the United States and narrowing the search down to a small town, noted Kurtz, who is assistant clinical director of the National Parkinson’s Foundation. “Now the challenge is to figure out the address of that person,” he said.
It is unclear how long that will take. In the case of Huntington’s disease, it took eight years to find the gene after researchers had progressed this far. For some other diseases, it was only a matter of months. “It depends on how much effort they will be able to devote to the project,” Kurtz added.
Scientists are still not sure, moreover, what percentage of Parkinson’s patients are encompassed by the finding.
The researchers studied DNA from 28 members of a large Italian family containing almost 600 people, more than 60 of whom have been diagnosed with Parkinson’s. The entire family traces its ancestry to a single Parkinson’s patient who lived in Contursi, a small Italian village near Salerno, in the 18th century.
Parkinson’s experts estimate that as many as 10% of all cases of the disease are genetic in origin, and they are confident that a gene isolated in one family will play a role in other families as well.
Most cases of Parkinson’s, Kurtz speculated, may be caused by a combination of genetic susceptibility and exposure to environmental toxins. The susceptibility could arise from the same gene that researchers are now pursuing or from one or more other genes, he said.
But Dr. Roger Duvoisin of the Robert Wood Johnson Medical School in New Brunswick, N.J., a co-author of the new report, is confident that the gene being sought will play a much larger role than many expect.
He told a Washington press conference Thursday that evidence suggests that heredity plays a major role in at least a quarter of all cases, and that after 30 years of poking around in his patients’ family trees, he believes that “all cases are genetic.”
Added Dr. C. Warren Olanow of the Mt. Sinai School of Medicine in New York City: “What is important is that this illustrates that a genetic linkage can be established in at least some patients. If we can carry it forward, it may give us a real clue to the mechanism of cellular degeneration, enabling us to introduce better therapies.”
Parkinson’s disease strikes about 60,000 people in the United States every year, according to Olanow. By some projections, he said, the number of afflicted Americans could quadruple, reaching 4 million by the year 2040.
The disease is characterized by tremors and rigidity in the limbs, slowness of movements and loss of muscle control, all of which worsen with age. As many as a third of patients also develop dementia, an impairment of thought processes.
Symptoms are caused by the death of brain cells that secrete a chemical called dopamine, which plays a key role in the transmission of commands from the brain to muscles. The disease is treated primarily with drugs or transplants that boost dopamine levels in the brain; there is growing evidence, Olanow said, that treatment early in the course of the disease can delay progression.
Early identification of patients through a genetic test--which is not yet available--would be a valuable contribution to therapy, he said.
The research on the Italian family was conducted by a team headed by Duvoisin and molecular biologist Mihael Polymeropoulos of the National Institutes of Health.
Looking at unique patterns of DNA in cells from the family members’ blood, the team has narrowed the search to a short region of Chromosome 4, one of the 23 pairs of chromosomes that make up the human genetic blueprint. “Once we started studying DNA from the families, we were able to [localize] the gene in a matter of weeks,” Polymeropoulos said. “Past disease-gene hunts have taken anywhere from years to decades.”
The segment they have found could contain more than 1,000 individual genes, however, so the team is not sure how long it will take them to identify it.
Meanwhile, they are beginning to look at other Parkinson’s-affected families to see if some of the same genetic markers on Chromosome 4 are present in their DNA as well. Confirmation that it is caused by the same genetic defect in other families would give the researchers confidence that the gene plays a crucial role in Parkinson’s.
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Parkinson’s Disease
Recent scientific discoveries pointing to a genetic cause for Parkinson’s disease offer hope for early detection and improved treatment. Here is a look at the disease.
IMPACT: The illness affects about 1 million Americans. Shown here are some of the prominent figures who have the disease.
CHARACTERISTICS: Physical rigidity, tremors and difficulty initiating movement.
CAUSE: Death of neurons in the brain that secrete dopamine.
TREATMENT: After the onset of symptoms, Parkinson’s patients typically survive 10 to 15 years. Conventional drugs that help symptoms early in the disease are less effective and have toxic side effects as the disease progresses.
Source: Times files
