Objective/Rationale:
This effort aims to use mass spectrometry analysis to detect and identify molecules present in a biological sample in its natural state (no dilution or extraction or other chemical work-up). The test will be very rapid (a few seconds) and will identify the molecules at trace levels. Sets of molecules like this can represent a snapshot of the state of the organism; they can represent a biomarker of disease and its progression. A minute amount of cerebrospinal fluid (CSF), less than five microliters, will be transferred to filter paper and sprayed into a mass spectrometer to measure the molecular masses and characterize the biomolecule constituents. This project aims to use the small molecules detected by paper spray in CSF as biomarkers for early diagnosis of Parkinson’s disease (PD).
Project Description:
Paper spray analysis will be coupled with advanced mass spectrometry to detect metabolite signatures. Compounds of particular interest will be targeted for in situ chemical derivatization to amplify their detection and allow accurate quantitative analysis. Statistical screening of the data will be used, and it will be validated by independent slower, but standard, methods. Phases of experiments are: (i) The paper spray mass spectrometry methodology will be developed using artificial CSF, (ii) human CSF samples will be used to optimize the methodology, and (iii) screening of a larger cohort of samples will be undertaken to validate the biomarker.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
There is a lack of sensitive and specific tests to allow clinicians to differentiate PD from other neural disorders with overlapping clinical symptoms. Furthermore, PD diagnosis in the early pre-motor symptom stages is crucial for preventing or slowing disease progression. Analysis of small samples of CSF by methods with sufficient sensitivity and molecular specificity should provide the detailed chemical information needed to diagnose PD in CSF samples.
Anticipated Outcome:
We anticipate to develop a rapid, sensitive assay for detection of PD in early stages of its development by analysis of CSF using mass spectrometry.