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."

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