Hi list, During my web wanderings yesterday, I came across the following on the National Institute of Environmental Health Sciences web site, outlining currently funded PD research at NIEHS. There's more PD information throughout the web site - the NIEHS homepage is: www.niehs.nih.gov I think it's very encouraging to see other NIH Institutes, in addition to NINDS, highlight PD research. Thanks to all the PD advocates, PD organizations, researchers and NIH officials who have worked together since early in 1999 to foster this type of collaboration. Parkinson's Disease Research at the NIEHS Parkinson's Disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's Disease. Most cases begin after the age of 50 and its incidence increases as a function of age. Like most diseases, PD appears to arise from the interaction of three events - an individual's inherited genetic susceptibility, their subsequent environmental exposures, and their age. Teasing apart the contributions of these individual factors in PD, as well as other diseases, is part of the mission of the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH). Genetic Contributions to PD: The relevance of genetic contributions to PD was the topic of a recent study by Dr. Caroline Tanner at the Parkinson's Institute and her colleagues. In this study of monozygous and heterozygous twins, researchers found that genetic susceptibility played a role in early-onset PD where symptoms are seen prior to age 50. In the vast majority of cases, though, where PD develops after age 50, genetics was not the determining factor. Presumably some other factor, possibly of environmental origin, accounts for the majority of PD in this country. Environmental Contributions to PD: Important insights into environmental triggers of PD were gained in the early 1980s when a synthetic heroin elicited severe Parkinsonism in addicts who injected it intravenously. The initiating agent was found to be 1-methyl-4-phenyl-1,2,5,6- tetrahydropyridine (MPTP), a compound with structural similarities to some herbicides and pesticides. Subsequent case-control studies have found increased incidence of PD associated with pesticide use, rural environments, consumption of well water, exposure to herbicides, and living near industrial plants, printing plants, or quarries. NIEHS Research on PD: In keeping with its public health mission, the NIEHS focuses on preventing development of PD by identifying environmental triggers of this disease and identifying how individuals differ in their susceptibility to these triggers. Additional research is directed toward defining the biochemical pathways of early PD development. Findings from such work could potentially lead to therapeutic interventions. An NIEHS-supported study at Wayne State University and the Henry Ford Hospital in Detroit has shown that long-term, occupational exposure to certain combinations of metals is significantly associated with acquiring PD. Mixtures of lead, copper and iron posed a greater risk than exposure to any of these metals singly. This is the first study to link long-term (20 or more years) occupational exposure to heavy metals with a chronic neurodegenerative disorder. NIEHS is sponsoring a study at the University of Washington investigating the consequences of exposure of genetically susceptible individuals to oxidative stressor environmental agents such as pesticides and heavy metals. This work is examining whether these agents, acting in concert with normal nervous system aging, increase PD risk. It is also looking at the genotypes of proteins responsible for the metabolism of some of these agents in the body to learn whether variations in their gene expression play a role in individual susceptibility to increased risk for PD. NIEHS is also supporting work at the University of Rochester to test the hypothesis that genetic determinants render dopaminergic neurons of the substantia nigra susceptible to neurotoxicant damage. To do this research, some of the neurons in normal mouse midbrain tissue will be genetically altered, creating a mosaic of normal and altered cells which will then be exposed to a relevant toxic agent to see whether the altered cells are selectively affected relative to normal neurons. Since PD is a malfunctioning of the dopaminergic systems of the brain, this work could have important implications in PD, as well as other neurodegenerative diseases, that operate through this mechanism. University of Georgia researchers, using a grant from NIEHS, are investigating the role of organochlorine pesticides in altering normal dopaminergic function using genetically-altered mice. This work has potential implications not only for PD, but also for other neurodegenerative diseases as well as some psychiatric disorders. NIEHS-supported researchers at Vanderbilt University are attempting to identify endogenous factors that start the neurodegenerative cascade leading to PD. These researchers hypothesize that heavy metal exposure could lead to oxidation of cathecholamines through a brain-specific pathway that produces a compound that is subsequently harmful to neurons. Exploring the gene-environment link, NIEHS-supported researchers at the University of Washington are examining why cigarette smoking reduces risk of PD by 50 percent. They have discovered that specific variants of monoamine oxidase B (MAO-B) in the brain greatly affected the protection afforded by cigarettes. Further exploration is ongoing to determine the significance of these genetic variants in affecting the risks of environmentally-caused PD. Additionally, the NIEHS is investigating the possibility of using its Agricultural Health Study to define environmental risks of PD. This study, done in collaboration with the National Cancer Institute, is a large cohort of farmers and pesticide applicators and their families. The NIEHS has worked with Dr. Tanner at the Parkinson's Institute to incorporate screening questions that could identify people in this cohort who should be further studied as potential PD cases. If a large enough subset is identified, it could lead to important insight into environmental triggers of PD. The NIEHS is interested in expanding its portfolio of research on PD. It has recently released a Program Announcement soliciting applications for research on environmental aspects of neurodegenerative diseases, including PD. The Institute also hopes to release a PD-specific Program Announcement later this year. NIEHS Fact Sheet 4/99 Our publications are not copyrighted and may be reproduced without permission. However, we do ask that credit be given to the National Institute of Environmental Health Sciences, National Institutes of Health. ------------------------------------------------------------------------ For further information on diseases related to the environment, please see: Alphabetical Listing of Health Topics Factsheets and Pamphlets Facts About Environment-Related Diseases and Health Risks NIEHS welcomes your comments and suggestions. Please send them to: WebCenter ([log in to unmask]) Page created: 27 April 99 Last revision: 01/07/00 ------------------------------------------------------------------------ ----------------------- The page was last updated Jan 7, 2000 - I suppose the PD-specific Program Announcement referred to in the last paragraph is forthcoming later this year, or does anyone know if it was already released? Linda Herman