First Early-detection Blood Test For Parkinson's Shows Promise
ScienceDaily (Mar. 12, 2008) - A test that profiles molecular biomarkers in
blood could become the first accurate diagnostic test for Parkinson's
disease, new research shows.
The screen relies on changes in dozens of small molecules in serum. These
"metabolomic" alterations form a unique pattern in people with Parkinson's
disease, according to a team led by researchers at the Weill Cornell Medical
College in New York City.
"A reliable blood test for Parkinson's disease would revolutionize not only
the care of people with this debilitating illness, it would facilitate
research as well," notes study senior author Dr. M. Flint Beal, chairman and
Anne Parrish Titzell Professor of Neurology at Weill Cornell Medical
College, and neurologist-in-chief at NewYork-Presbyterian Hospital/Weill
Cornell Medical Center.
According to the National Parkinson Foundation, an estimated 1.5 million
Americans have the neurodegenerative disease, and 60,000 new cases are
diagnosed each year. Actor Michael J. Fox, boxer Muhammad Ali, and former
U.S. Attorney General Janet Reno all suffer from Parkinson's, which strikes
men and women in roughly equal numbers.
"Right now, a Parkinson's diagnosis is made solely on a clinical review of
symptoms - we have no biologic test," notes Dr. Beal. At best, a
symptom-based screen is still only 90 percent accurate, he adds.
"That can cause real problems, because that remaining 10 percent of
patients - who may have look-alike conditions such as multi-system atrophy
or progressive supranuclear palsy - end up getting treated with Parkinson's
drugs," Dr. Beal says. "These medicines may appear to help them a little
while, but in the meantime, they haven't been getting the treatment that's
necessarily best for them."
An early-detection test would also be enormously useful in tracking the
health of patients who may be at higher risk for Parkinson's, such as those
with a family history of the disease.
Finally, the integrity of clinical trials is undermined by the lack of an
accurate screen, Dr. Beal notes. "Every time you do a clinical trial into
Parkinson's and you have patients that are misdiagnosed, it enters 'noise'
into the analysis, skewing the results. A truly reliable test could help
eliminate that," the researcher notes.
That's why encouraging results for the new test - based on a patient's
"metabolomic profile" - are so important.
Metabolomics is the study of changes in thousands of distinct, very small
molecules found in body fluids or tissues. "Anytime you have a genetic or
environmental perturbation, these molecules are altered in specific ways,"
Dr. Beal explains.
Because Parkinson's treatment could itself trigger some of these
alterations, the researchers first compared metabolomic patterns in the
blood of Parkinson's patients who were not undergoing treatment versus those
who were medicated. "That gave us a 'medication-free' profile that we could
use going forward," Dr. Beal explains.
In the next stage of the research, the team compared blood samples from 66
patients with Parkinson's disease against 25 healthy controls (most of whom
were the patients' spouses). The metabolomic analysis included over 2,000
small molecules found in the blood.
"We discovered a clear differentiation between the metabolomic profiles of
the Parkinson's disease patients versus those of the controls," Dr. Beal
says. "No one molecule was definitive, but a pattern of about 160 compounds
emerged that was highly specific to Parkinson's patients."
The significance of many individual compounds to the disease remains unknown
and will be the focus of future study. But changes in a few well-known
metabolites linked to oxidative stress were clearly linked to Parkinson's.
These included low levels of the antioxidant uric acid; an increase in blood
levels of another antioxidant, glutathione; and increased levels of a marker
for oxidative damage called 8-OHdG.
"Together, these and other compounds were arranged into a metabolomic
pattern that identified Parkinson's disease with great accuracy," Dr. Beal
says.
He stressed that more work needs to be done to validate the finding, and a
test that might be used routinely by doctors is still a few years away.
"We are currently enlarging the sample size and studying people at serial
intervals, to see if this test might also serve as a benchmark for disease
progression," Dr. Beal says. "We are also looking at people who carry a gene
for a familial form of Parkinson's, but who do not have the illness now. We
hope to track them over time to see if this metabolomic profile is
predictive of disease onset."
If those data prove as promising as this early trial, an early-detection
blood test for Parkinson's disease could someday become a reality. According
to Dr. Beal, "That would be a big step forward for both the treatment and
the study of this devastating illness."
Findings are published in the journal Brain. Co-researchers include lead
researcher Dr. Mikhail Bogdanov, of Weill Cornell Medical College and
Bedford VA Medical Center, Bedford, Mass.; Dr. Wayne R. Matson, of Bedford
VA Medical Center; Dr. Lei Wang, of Weill Cornell and Bedford VA Medical
Center; and Dr. Rachel Saunders-Pullman and Dr. Susan S. Bressman, of Albert
Einstein College of Medicine, New York City.
This work was supported by the Michael J. Fox Foundation, the Department of
Defense, and Edwin and Carolyne Levy.
Adapted from materials provided by Weill Cornell Medical College.
Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
rbrown@xxxxxxxxx
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