Metabolomic Analysis of Parkinson's Disease Cerebrospinal Fluid
Clinicopathological Correlations of Parkinsonís Disease, 2009
Metabolomic analysis is a state-of-the-art laboratory technique and computerized analysis used to catalog hundreds of the chemical constituents in the brain environment. We will work with specimens from the Arizona Parkinson’s Disease Consortium (APDC) to discover Parkinson’s disease biomarkers – substances that permit PD to be differentiated from controls, and that may offer better diagnostic tools as well as insights into the cause(s) of this disorder.
Metabolomic analysis separates several hundreds of the approximately 2,500 chemical compounds found in the human body. Though many are present only in minute quantities, they may provide valuable clues to the origins of Parkinson’s disease and its diagnosis. Our initial work found distinctive changes in compounds termed purines in Parkinson’s disease cerebrospinal fluid. For the upcoming project, detailed measurements will be carried out in several dozen APDC specimens to discover unique patterns of change in Parkinson’s disease. The analytical techniques are termed high-performance liquid chromatography coupled to mass spectophotometry. Measurements from this system enter into a computerized relational database that can be explored for thousands of combinations that, potentially, might offer better options for diagnosis and understanding of Parkinson’s disease.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Today, no blood test or other screening tool provides unequivocal diagnosis of Parkinson’s disease. Reliable testing to detect the earliest stages of the disorder are needed (perhaps even before symptoms emerge) if effective neuroprotective treatments are developed. A biomarker specific to Parkinson’s disease also might provide a target that could be utilized in therapeutics research.
We hope to confirm previous findings that certain purine compounds can differentiate Parkinson’s disease subjects from healthy controls. The planned metabolomic analysis will also explore for untargeted compounds and relationships among groups of compounds in the search for relevant biochemical clues. The same methods have been useful in finding disease-specific markers for other disorders, and we anticipate the unique specimen and data resources of the APDC will permit similar gains.
Although it might seem the most logical way to diagnose Parkinson’s disease (PD), a laboratory test has not been developed from measurements targeting dopamine, which is the brain signaling chemical (neurotransmitter) deficient in this disorder. Consequently, we used state-of-the-art laboratory testing called metabolomic analysis. This technique was used to separate and measure minute amounts of several hundred chemicals present in cerebrospinal fluid (CSF) to aid in the search for PD biomarkers (diagnostic tests). From this work, we discovered several compounds that distinguished quite effectively between PD and normal controls (and with a high degree of statistical significance). Curiously, none of these substances have been previously implicated in the cellular degeneration of the PD brain. We plan to replicate this work and with the same methods used in this study we hope to find peripheral biomarkers (blood or urine tests) useful for diagnostic screening. These biomarkers may also offer insight into the disease process of PD.
Presentations & Publications
This work will be published as an abstract in an upcoming 2011 issue of the journal MOVEMENT DISORDERS, an international publication sent to the Parkinson’s disease clinical and research community. It will also be presented as a poster at the International Congress of the Movement Disorder Society in Toronto during June, 2011. Subsequently, the data will be reported in more detail in an article to be sent to a pee-reviewed journal for publication.
Director, Parkinsonís Disease and Movement Disorders Program at Henry Ford Hospital
Professor of Neurology at Wayne State University School of Medicine
Location: West Bloomfield, Michigan