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Blood-Based Biomarkers May Lead to Earlier Diagnosis of Parkinson's Disease

20 January 2013 IOS Press

Pilot Study Published in the Journal of Parkinson's Disease

Amsterdam, NL, 20 January 2013 - Parkinson's disease (PD) is a progressive
neurological condition. At present, it is usually diagnosed only when motor
features are present. Hence, there is a need to develop objective and
measurable biomarkers to improve PD diagnostics during its earlier stage,
prior to its motor onset. In this pilot study, researchers identified and
tested the first blood-based circulating microRNA (miRNA) biomarkers for PD.
Their results are published in the latest issue of Journal of Parkinson's

PD is the second most common neurodegenerative disorder in the United
States, affecting approximately one million Americans and five million
people worldwide. Its prevalence is projected to double by 2030. The most
obvious symptoms are movement-related, such as involuntary shaking and
muscle stiffness; later, cognitive and behavioral problems may develop along
with additional peripheral symptoms such as gastrointestinal dysfunction.
There is currently no cure, although the drug levodopa can relieve the
symptoms. The differential diagnosis of PD is based primarily on subjective
clinical rating scales associated with motor functions. As these scales can
only be used when motor features are present, 60-70% of a patient's
dopaminergic neurons are already lost by the time of diagnosis.

"The ideal biomarker should be minimally-invasive, cost efficient,
quantifiable, reproducible, specific, and sensitive," explains lead
investigator Sok Kean Khoo, PhD, of the Center for Neurodegenerative Science
and Genomic Microarray Core Facility at the Van Andel Institute, Grand
Rapids, Michigan. "Biofluids such as plasma could provide an ideal resource
for development of such desirable biomarkers. However, clinical diagnostic
tests based on biochemical analysis of biofluids from PD patients have yet
to be established," she continues.

Investigators hypothesized that specific miRNAs related to PD can be
detected in plasma. It is known that miRNAs detected in various cells and
tissues can also be found in biofluids such as blood plasma and serum. A
preliminary study using miRNA microarrays showed that approximately 4%
(35/866) of miRNAs from healthy brain tissues could also be detected in the
plasma of healthy controls.

In an initial study they obtained the global miRNA expressions in plasma of
an initial discovery set of 32 PD patients and 32 normal controls and
identified nine pairs of PD-predictive classifiers and 13
most-differentially expressed miRNAs as potential biomarkers to discriminate
PD patients from normal controls. They then used a quantitative real-time
Polymerase Chain Reaction technique (qRT-PCR) to validate and evaluate the
performance of these biomarkers in a new replication set of 42 PD patients
and 30 controls from the same clinical site.

They then identified a combination of biomarkers that achieved the highest
predictive performance and applied this panel of biomarkers to a new,
independent validation set of samples from 30 PD patients from a different
clinical site, which showed lower biomarker performance.

The investigators acknowledge that there are still challenges to be overcome
in validating biomarker candidates due to clinical and sample variability
and factors that influence miRNA expression such as comorbidities and other
medication the patient is taking. However, explains Dr Khoo, "This is a
proof-of-concept study to demonstrate the feasibility of using plasma-based
circulating miRNAs, and the hypothesis that miRNA expression changes are
associated with the neurodegenerative disease process, either directly or as
part of positive feedback loops, is emerging rapidly. This study opens new
opportunities to the exploration of circulating miRNAs for diagnostic,
prognostic, and therapeutic interventions for PD and possibly other
neurodegenerative diseases."

"A diagnostic test to determine the status of a patient's disease onset
would provide crucial data for more timely, efficient, and successful
therapeutic interventions," said Patrik Brundin, MD, PhD, Director of Van
Andel Institute's Center for Neurodegenerative Science. "There is an urgent
need to develop objective, measureable biomarkers to improve PD diagnostics
and help define its subtypes, and Dr. Khoo's interesting study is an
important step in that direction."

Research was supported by the Van Andel Research Foundation, Van Andel
Institute's Purple Community: 100% Hope, the Swedish Medical Research
Council, the Erling-Persson Family Foundation, the Swedish Parkinson
Foundation, the Swedish Parkinson's Disease Association, and The Michael J.
Fox Foundation for Parkinson's Research Rapid Response Innovation Award.

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