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Elevated urate levels may slow the
progression of Parkinson's disease
Mass. General, Harvard School
of Public Health study may lead to new therapy
BOSTON - April 14, 2008 - Naturally elevated levels of the
antioxidant urate may slow the progression of Parkinson's disease
in men. Researchers from the MassGeneral
Institute for Neurodegenerative Disease (MGH-MIND) and Harvard
School of Public Health (HSPH) examined data from an earlier
study and found that, among recently diagnosed Parkinson's patients,
those with the highest urate levels had a significantly slower rate
of disease progression during the two-year study period. The report,
which will appear in the June 2008 Archives of Neurology
and is receiving early online release, may lead to urate-based therapies
for the disorder.
Parkinson's disease - characterized by tremors, rigidity, difficulty
walking and other symptoms - is caused by the destruction of brain
cells that produce the neurotransmitter dopamine. Several epidemiologic
studies, including the HSPH-based Health Professionals Follow-up
Study, have found that healthy people with elevated levels of urate,
a normal component of the blood, may have a reduced risk of developing
Parkinson's disease.
"Because the neurodegenerative process that leads to Parkinson's
disease starts years before the onset of symptoms and progresses
throughout the disease course, we reasoned that blood urate could
be slowing the rate of neurodegeneration and hypothesized that urate's
beneficial effect might extend beyond the time of diagnosis,"
says Alberto Ascherio, MD, DrPH, of HSPH, the study's senior author.
To investigate this hypothesis, the MGH/HSPH team analyzed information
from the PRECEPT trial conducted by the Parkinson Study Group, based
at the University of Rochester. That study followed a group of recently
diagnosed Parkinson's patients to see if an experimental medication
could delay disease progression, measured by the need to begin standard
drug therapy and by imaging of the brain structures that produce
dopamine. Blood samples from about 800 PRECEPT trial participants
were analyzed for urate levels, which were compared to information
about symptom progression of the trial participants and the imaging
study results.
The results showed that participants with the highest urate levels
at the beginning of the study had about half the risk of needing
to start Parkinson's treatment drugs as did those with the lowest
levels. The brain scans indicated that participants with higher
urate levels also lost the fewest dopamine-producing neurons. The
association of urate levels with risk of progression was seen both
in those receiving the drug studied in the PRECEPT trial - which
did not have significant results - and in the placebo group. Men
are known to have higher urate levels, and since there were only
a few women among those with elevated urate, results of the current
analysis were not significant for women. The potential of urate
to treat female Parkinson's patients needs to be investigated in
future studies, the researchers note.
"These findings, combined with prior knowledge of urate's
protective properties in laboratory studies, raise the possibility
that urate-elevating strategies could be used to slow the neurodegeneration
of Parkinson's disease," says Michael Schwarzschild, MD, PhD,
of MGH-MIND, the study's lead author. "Potential benefits of
urate have to be tempered against the known risks of elevated urate
levels, which include gout and kidney stones. From what we know
now, urate elevation should only be attempted in the context of
a closely monitored clinical trial, in which potential benefits
and risks are carefully balanced."
Schwarzschild and Ascherio, with an award from The
Michael J. Fox Foundation for Parkinson's Research, are teaming
up with Parkinson Study Group doctors from across the country to
conduct a multicenter Phase 2 trial, being announced by the Foundation
today. Ninety people newly diagnosed with Parkinson's but not yet
needing treatment will be treated with the urate precursor inosine
or a placebo. Information about trial enrollment will be available
later this year at www.pdtrials.org.
Schwarzschild is an associate professor of Neurology at Harvard
Medical School and Ascherio is an associate professor of Nutrition
and Epidemiology at Harvard School of Public Health. Additional
co-authors of the report are Steven Schwid, MD, Arthur Watts, PhD,
David Oakes, PhD, and Ira Shoulson, MD, University of Rochester;
Kenneth Marek, MD, Institute for Neurodegenerative Disorders, New
Haven, Conn.; and Anthony Lang, MD, Toronto Western Hospital. The
Archives of Neurology study was supported by grants from the National
Institutes of Health and the Beeson Scholars Program of the American
Federation for Aging Research.
Harvard School of Public Health is dedicated to advancing the public's
health through learning, discovery, and communication. More than
400 faculty members are engaged in teaching and training the 1,000-plus
student body in a broad spectrum of disciplines crucial to the health
and well being of individuals and populations around the world.
Programs and projects range from the molecular biology of AIDS vaccines
to the epidemiology of cancer; from risk analysis to violence prevention;
from maternal and children's health to quality of care measurement;
from health care management to international health and human rights.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $500 million
and major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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