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
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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