|Investment in Parkinson's Disease Data
Bank Yields Potential Therapy
Individuals with Parkinson's disease who have higher levels of
a metabolite called urate in their blood and in cerebrospinal fluid
(CSF) have a slower rate of disease progression, according to a
study funded by the National Institutes of Health. A clinical trial
is under way to examine the safety and potential benefits of supplemental
urate elevation for recently diagnosed Parkinson's patients who
have low urate levels.
Investigators demonstrated the link with urate by mining a repository
of clinical data and tissue samples collected from Parkinson's
patients more than 20 years ago as part of a pioneering study called
DATATOP, funded by NIH's National Institute of Neurological Disorders
and Stroke (NINDS). The new study appears in Archives of Neurology.
It was funded primarily by NINDS, with additional support from
the Department of Defense and private organizations.
"This study speaks to the value of saving data and biospecimens
from large clinical studies, and making them available to the research
community to pursue new, unanticipated ideas," said Michael
Schwarzschild, M.D., Ph.D., an associate professor of neurology
at Massachusetts General Hospital in Boston, who lead the study
together with Alberto Ascherio, M.D., Dr.PH, a professor of epidemiology
and nutrition at the Harvard School of Public Health.
Experts emphasize there is no proof that elevating urate levels
will help against Parkinson's disease, and that it should not be
attempted outside of a clinical trial, where physicians can closely
monitor possible benefits and risks, such as gout and heart disease.
Parkinson's disease attacks cells in the brain that regulate movement
by releasing a chemical called dopamine. The loss of those cells
leads to progressively disabling symptoms, including involuntary
shaking, slow movement, stiffened muscle tone, and impaired balance.
Levodopa, a precursor of dopamine, provides some relief from those
symptoms but does not alter the disease course.
"Effective treatments for Parkinson's disease have been elusive.
By taking a fresh look at the repository of clinical data and stored
samples from the two-decade old DATATOP trial, this study has identified
urate as a biomarker for the progression of the disease and suggests
a potential new pathway for targeted therapy development," said
Margaret Sutherland, Ph.D., a program director at NINDS.
Urate (or uric acid) is a product of the body's metabolism. Diets
high in liver, seafood, and dried beans and peas tend to cause
higher levels of urate in the blood, and are also associated with
gout — a painful buildup of urate crystals in the joints.
Urate is a natural antioxidant, and many studies have found that
antioxidants slow the course of Parkinson's disease in animal models.
Also, prior research from Dr. Ascherio's epidemiology group has
shown that people who have gout or who consume foods associated
with high urate have a lower incidence of Parkinson's disease.
Drs. Ascherio and Schwarzschild and their collaborators in the
Parkinson Study Group are the first to examine whether urate levels
are related to the course of Parkinson's disease. Last year, after
mining data from another large clinical trial, they reported that
high levels of urate in blood were associated with a slower disease
course. The new study is an expansion of that work and the first
time that investigators have looked for a connection between the
course of Parkinson's and levels of urate in CSF, the fluid that
fills spaces in the brain and spinal cord.
The DATATOP trial began in the late 1980s, and was designed to
test whether vitamin E, the drug deprenyl (selegiline), or a combination
of both could slow the course of early-stage Parkinson's disease.
The trial enrolled 800 patients and followed them for two years.
Deprenyl, which inhibits the breakdown of dopamine, was found to
provide short-term relief from symptoms. Vitamin E showed no significant
As part of the DATATOP trial, samples of blood and CSF were acquired
from more than 90 percent of the participants at enrollment. In
the new study, the researchers analyzed whether blood and CSF urate
levels were related to the course of Parkinson's by relying on
blood measurements done at the time of the DATATOP trial and by
taking new measurements from the 20-year-old, frozen samples of
Looking across all of the treatment groups in the study, the researchers
found that patients with the highest urate levels in their blood
and CSF had a slower functional decline as measured by their need
for levodopa treatment. The results suggest that urate elevation
might slow the course of Parkinson's in patients with early-stage
disease and low urate levels.
The Safety of URate Elevation in Parkinson Disease (SURE-PD) study,
led by Dr. Schwarzschild, is a placebo-controlled trial designed
to test that hypothesis. Patients in the treatment arm of the trial
will take daily, oral doses of a urate precursor called inosine
for up to two years. The trial is funded by the Michael J. Fox
Foundation, and is recruiting recently diagnosed patients who do
not yet require Parkinson's medication at 11 sites across the United
States. For more information, visit www.clinicaltrials.gov and
search by the identifier NCT00833690.
For more information about Parkinson's disease, visit http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm.
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Reference: Ascherio A et al. "Urate as a Predictor
of the Rate of Clinical Decline in Parkinson Disease." Archives
of Neurology, published online October 12, 2009.