Here is the article I referenced in previous post:
Peace, John
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Friday June 27
Daily Science News
Media Release
Contact: Jeff Witherly
301-402-8564
[log in to unmask]
National Human Genome Research Institute
NIH Researchers Find First Parkinson's Disease Gene
Bethesda, MD -- Scientists at the National Human Genome Research
Institute (NHGRI) at the National Institutes of Health (NIH) have for
the first time precisely identified a gene abnormality that causes some
cases of Parkinson's disease. The gene spells out instructions for a
protein called alpha synuclein. In the abnormal version of the gene, the
researchers found a mutation in a single base pair-one incorrect letter
in the string of more than 400 that compose the instructions for making
the protein. Because the normal gene plays a role in the function of
nerve cells, the finding gives researchers a powerful new tool for
understanding cellular abnormalities in Parkinson's disease and
demonstrates a connection between Parkinson's disease research and
research into other neurological disorders, such as Alzheimer's disease.
The research report appears in the June 27 issue of the journal Science.
According to NHGRI's Dr. Mihael Polymeropoulos, the paper's lead author,
"the finding opens completely new horizons in understanding the disease
and interpreting the biology of the illness. Moreover, the finding will
have an application in the not too distant future as a clinical research
tool within families especially prone to Parkinson's disease and may
permit us to design clinical studies for investigating drugs or other
ways of postponing or offering protection from the illness."
The paper confirms last fall's report-co-authored by the same NHGRI
team-that a predisposition to at least one form of Parkinson's disease
is inherited and that the gene responsible was situated somewhere in a
large region on the long arm of chromosome 4. Until that report, most
experts believed that Parkinson's disease was probably due to unknown
factors present in the environment.
Parkinson's disease afflicts about a 500,000 people in the United States
alone, with about 50,000 new cases reported every year. Its hallmark is
shaking or trembling of a limb and, in the later stages, a slow,
shuffling walk and stooped posture.
Parkinson's disease is a common progressive neurological disorder that
results from loss of nerve cells in a region of the brain that controls
movement. This degeneration creates a shortage of the brain signaling
chemical-dopamine-causing impaired movement. When symptoms grow severe,
doctors usually prescribe levodopa (L-dopa), which helps replace the
brain's dopamine.
"This finding could prove to be the most significant advance in our
understanding of Parkinson's disease since the dopamine hypothesis was
put forward in the mid 1960s. It is a good example of how we make
progress towards the conquest of particular diseases by supporting a
diversity of fundamental and clinical research. This discovery about
Parkinson's disease also deepens our study of Alzheimer's disease, basic
neuroscience, cell biology, and genome research and gene mapping," says
NIH director, Dr. Harold Varmus.
To find the gene, the scientists first studied members of a large family
that came originally from Italy. Some had emigrated to the US early in
this century, and more than 60 family members on both sides of the
Atlantic have been diagnosed with Parkinson's disease. Efforts to locate
the gene intensified after a workshop on Parkinson's disease sponsored
by the National Institute of Neurological Disorders and Stroke (NINDS).
At that meeting, which identified genetic research as an important area
of opportunity, scientists from NIH met researchers at the Robert Wood
Johnson Medical School in Piscataway, New Jersey, who had been
investigating Parkinson's prone families for some time. Soon after, the
NIH scientists, led by Dr. Polymeropoulos, began to carry out a genetic
analysis of Parkinson's disease using DNA from patients identified and
followed by an international team of researchers, including the Robert
Wood Johnson team and physicans at the University of Naples, Italy. With
the help of collaborators at the University of Patras Medical School in
Greece, the NHGRI researchers also studied five additional unrelated
families of Greek origin with a hereditary form of the disease.
Using information provided by the Human Genome Project, NHGRI
researchers rapidly located the mutation to a region of the genome
containing approximately 100 genes. One of the genes already placed in
this interval was alpha synuclein. The alpha synuclein gene was an
excellent candidate for being a Parkinson's disease gene because
previous research had already shown that the amyloid plaques of
Alzheimer's disease patients contained fragments of the alpha synuclein
protein. Considering its potential role in neurodegenerative disease,
the researchers began looking at the precise sequence of alpha synuclein
in normal and affected individuals. In the Italian family and three of
the Greek families, the Parkinson's patients were found to possess an
identical mutation in a single base pair of the alpha synuclein gene.
Parkinson's disease is characterized by deposits in the brain called
Lewy bodies. The researchers hypothesize the mutation in the synuclein
protein causes it to aggregate, thus attracting other proteins to form a
deposit that damages the cell. A similar mechanism has been proposed for
the production of amyloid plaques in Alzheimer's disease. The finding
that Alzheimer's disease plaques contain a fragment of alpha synuclein
further strengthens the idea that a common mechanism may be operating in
both of these neurodegenerative diseases.
The NHGRI researchers suspect that the abnormal gene is responsible for
a significant portion of familial Parkinson's disease with onset
generally before the age of 60. It is not known how frequent alterations
in this gene will be in later onset cases with less striking family
history, though the same pathway which has been identified to be
involved in these four families may turn out to be abnormal in other
patients as well. Alpha synuclein is actually a member of a group of
similar synuclein genes in the human genome. The NHGRI scientists are
now actively searching among patients with familial Parkinson's disease
who do not possess this alpha synuclein mutation for mutations in those
other synuclein genes. The alpha synuclein gene, and other similar genes
known to exist in the human genome, are expected to help scientists
decipher additional causes of Parkinson's and perhaps shed light on
other devastating and common brain disorders.
"For people with Parkinson's disease, this is a small but important step
in a very long journey-hopefully leading to an understanding of the
basic underlying defect in Parkinson's disease which causes in the death
or loss of function of the cells in the brain. If it results in a deeper
understanding of how Parkinson's disease comes about, it may make us
much smarter in developing therapies. But it is important to stress that
at this point there is no direct therapeutic result from this finding,"
says the paper's senior author, NHGRI's Dr. Robert Nussbaum.
Although the researchers caution that a test will provide limited
information for most people, one near-term application for such a test
in high-risk families will be in research aimed at developing ways of
slowing or stabilizing the illness. Investigators are hoping that such
preventive measures will eventually be useful in treating Parkinson's
disease.
The discovery of the mutant alpha synuclein gene raises issues of
genetic testing that have become increasingly familiar as the list of
gene discoveries lengthens. The issues are especially similar to those
that have arisen in connection with genetic testing for predisposition
to other diseases that appear late in life, notably Alzheimer's disease
and Huntington's disease.
"Discoveries like this reflect how rapid disease gene identification can
be as the Human Genome Project has continued to mine the genome for its
treasures," says NHGRI director Dr. Francis Collins. "As more gene sites
are identified, it will become almost routine for disease gene hunters
to find an already characterized gene waiting for them when they arrive
at the neighborhood they know is involved in a disease. But this
discovery, which raises the possibility of identifying healthy
individuals at future risk for illness, also underlines again how
crucial it is the provide legislative protections against misuse of the
information, especially in health insurance and employment."
"The results announced today highlight the importance-and benefit-of
bringing new ideas into the field of Parkinson's disease research," says
Dr. Zach W. Hall, Director of the NINDS. "The identity of this gene
suggests an important new link between Parkinson's and Alzheimer's
diseases, and may ultimately help us prevent or delay the cell death
that is responsible for degenerative brain disease."
NHGRI oversees the NIH's role in the Human Genome Project, an
international research effort to develop tools for gene discovery.
------------------------------------------------------------------------
Press contact information:
For interviews with Drs. Mihael Polymeropoulos or Robert Nussbaum of the
National Human Genome Research Institute, contact Jeff Witherly or Galen
Perry at (301) 402-8564 or -3035.
For interviews with Dr. Francis Collins, Director of the National Human
Genome Research Institute, contact Sharon Durham or Leslie Fink at (301)
402-0911.
For interviews with Dr. Zach Hall, Director of the National Institute of
Neurological Disorders and Stroke; Parkinson's patients or Parkinson's
support group, contact Marian Emr at (301) 496-5924.
The NHGRI website is located at: http://www.nhgri.nih.gov/
The NHGRI website will carry the press conference in audio form at 4 pm
June 26th. The website will also have additional information on the
research, research teams, prior Parkinson's disease research
announcements, related links and public and media information on genetic
research, genetic testing and the Human Genome Project. For broadcast
media, downloadable broadcast quality AIFF. Electronic media will
receive laboratory B-roll at the press conference which includes
explanatory statements on the finding by Drs. Polymeropoulos and
Nussbaum.
