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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.

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