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>From Newsday, Friday, October 11, 1996 By Jamie Talan STAFF WRITER Parkinson's disease may be caused by a genetic defect in the body's energy-producing cells, a finding that could lead to treatments to stall or prevent the debilitating disorder, according to a new study. Researchers at the University of Virginia are defying conventional genetic wisdom, suggesting that a mutation in mitochondrial DNA, rather than in the DNA that makes up chromosomes, can lead to common medical disorders like Parkinson'S. The disease leaves people with tremors and rigidity. Dr. W. Davis Parker, a professor of neurology and senior author of the Parkinson's study, said his team is looking at a variety of common illnesses that could be triggered by mitochondrial mutation. Parker's team has also identified a similar genetic process in patients with Alzheimer's. "This is big news," said Dr. Flint Beal, a professor of neurology at Harvard Medical School, "This is the best scientific proof available that suggests that a genetic mutation leads to Parkinson's," Parkinson's disease affects about 2 million Americans. It has long been a puzzle to investigators because it did not seem to run in families. Therefore, a genetic link was not expected. Mitochondria are the thousands of thread-like bo dies in each cell that contain enzymes that control the production of energy. It's the cell's breathing machine, gathering oxygen to use as energy. Mitochondria has its own DNA, inherited solely from the mother. Parker and his colleagues decided to look at genetic defects in mitochondrial DNA in patients with Parkinson's, based in part on research done a decade ago. The earlier research had studied several young drug addicts who had developed Parkinson's after exposure to heroin tainted with the environmental toxin MPTP. The study found MPTP had triggered a defect in the mitochondrial enzyme called complex 1, whose job is to shuttle energy through the cell. In Parker's first experiments, 10 patients with Parkinson's had about a 50 percent decrease in this enzyme compared to those who didn't have the disease. "It was the first time anyone had ever seen this in a common disease," said Parker. Other mitochondrial mutations have been described only in rare human diseases. That this enzyme exists in every cell in the body suggests that Parkinson's is a systemic problem and not just a brain disease, he said. "You can find this defect all over the body." Scientists are now trying to understand how the mutation, which causes a depletion of complex 1, leads to death of dopamine neurons in the brain region called the substantia nigra. Dopamine is a chemical in brain cells that regulates movement and other behavior. But even though complex 1 was deficient in the blood of patients, it didn't prove that Parkinson's was a genetic disease, he said. In the latest study, published today in the Annals of Neurology, Parker went back to the lab and exposed the patients' blood cells to a human neuro blastoma, a cell line used in research because of its ability to replicate quickly, and then cleared the line of its own mitochondrial DNA. Then, Parker and his team did the same experiment using blood cells from people without the disease. When the cells divided, they found that the Parkinson's cell line produced the genetic defect, reduced complex 1. The decreased level of complex 1 led to an increase in the production of oxygen-free radicals, scavenger cells that set in motion programed cell death. This process could explain how brain cells slowly die away, causing more symptoms. "We are working toward a general principle in human genetics," said Parker. "These genes have been looked upon as very unimportant in human disease. I am sure these findings will be controversial, but we think this process may influence many diseases." The study does not rule out the influence of environmental toxins as a trigger for Parkinson's. The researchers have also exposed the experimental cell lines to the toxin MPTP and found a more enhanced production of cell-damaging oxygen-free radicals. The researchers have not identified the precise mutation, yet. Parker has expanded his studies to include about 35 patients. A19 Margaret Tuchman(54yrs,dx1980) [log in to unmask] *******************************************************************