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FROM: Medical Industry Today November 15, 2001, Thursday SECTION: WORLD HEALTH HEADLINE: Duke Study: Parkinson's Strongly Linked to Genetics " A genomic screen of Parkinson's disease suggests that multiple genes are involved in the origins of the most common form of the disease that occurs later in life, Duke University Medical Center researchers announced in a statement Wednesday. The findings provide strong evidence that Parkinson's disease has an important genetic component and is not caused exclusively by environmental factors, said Margaret Pericak-Vance, director of Duke's Center for Human Genetics and senior author of the study that appears in the Nov. 13 issue of the "Journal of the American Medical Association." The new findings challenge the results of previously published studies of twins that suggested environmental factors are the primary cause of Parkinson's disease. While most scientists agree there is a genetic link, the consensus has been that it is mostly in the rare, early-onset form of the disease in people diagnosed before age 40. Parkinson's disease, a disorder of the nervous system that causes tremors and muscular rigidity, affects more than 1 million people in the United States, according to the researchers. "Like many complex traits, it's likely that Parkinson's disease is caused by a web of interacting genetic and environmental risk factors, in which specific genetic templates are more susceptible to the influences of environmental exposures. Further studies to identify the molecular pathways affected by the responsible genes will provide invaluable insight into the complex etiology and potential treatment of Parkinson's disease," Pericak-Vance said in a statement. Duke researchers led a team from 16 institutions across the United States and Australia searching for families with one or more members with Parkinson's disease. The researchers identified 174 families and collected blood samples from as many members as possible to conduct genetic analyses to spot any common genetic factors that might confer susceptibility to Parkinson's. The study provides strong evidence that several genes may influence the development of late-onset Parkinson's and that age at onset and response to the commonly prescribed drug levodopa may be useful discriminators for genetic origins of Parkinson's. The researchers detected evidence for genetic linkage to five distinct regions on chromosomes 5, 6, 8, 9 and 17. Chromosome 6 contains the Parkin gene, which was previously thought to be involved only in the rare early-onset form of Parkinson's. The researchers discovered Parkin mutations in 18 families with both late- and early-onset cases of Parkinson's. In families with late-onset Parkinson's, the strongest overall evidence for linkage was on chromosome 17 near the tau gene, which was previously shown to be involved in other neurodegenerative diseases. Tau was not previously thought to be involved in the common form of Parkinson's. The linkage and mutation results indicate that Parkin is indeed an important genetic factor in Parkinson's and mutations are more prevalent than previously reported, Pericak-Vance said. The researchers discovered Parkin mutations in 11 early-onset and seven late-onset families. The researchers conducted a complete genomic screen of 174 U.S. and Australian families in which two or more family members had the late- or early-onset forms of Parkinson's. Researchers studied 870 family members, 378 of which were diagnosed with Parkinson's; 379 were unaffected by Parkinson's and 113 had an unclear affection status. The affected individuals were defined as those who possess at least two signs of Parkinson's, such as rest tremor, bradykinesia (slowness of movement) and rigidity, but have no atypical clinical features or other causes of Parkinson's. Unclear individuals had only one sign and/or had a history of atypical clinical features, and unaffected individuals had no signs of Parkinson's. In the 147 families with late-onset Parkinson's disease, the strongest overall evidence for linkage was on chromosome 17 near the tau gene. The evidence for linkage of late-onset Parkinson's to chromosome 17 suggests a possible genetic link between Parkinson's, frontotemporal dementia with parkinsonism (FTDP) and progressive supranuclear palsy (PSP), which is a rare neurological disorder related to Parkinson's, the researchers said. In October 2000, the Pericak-Vance research team demonstrated for the first time that the alteration of a specific gene on chromosome 6 appears to contribute to both the common late-onset form of Parkinson's and the rarer, early-onset form of the disease. In a 1998 study, Japanese researchers reported that the mutation of the gene on chromosome 6, called the Parkin gene, was responsible for autosomal recessive juvenile parkinsonism, a disorder similar to, but considered distinct from Parkinson's. The Duke study suggests that the Parkin gene is important in early-onset Parkinson's, and that multiple genetic factors may be important in the development of late-onset Parkinson's. These results should initiate additional analyses to identify new mechanisms and genes that increase susceptibility to Parkinson's, Pericak-Vance said. The cause of Parkinson's disease is unknown, but it is thought to have both genetic and environmental factors. Past research has shown that environmental factors, such as exposure to pesticides, may contribute to development of Parkinson's in genetically susceptible individuals. Other research, such as a 1999 study by the Parkinson's Institute in Sunnyvale, Calif., in which 172 twins were studied, offered evidence for environmental factors. The study was funded by grants from the National Institutes of Health and by GlaxoSmithKline." ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn