Objective/Rationale:
Based on our earlier findings that yielded several promising biomarkers, this metabolomic study of small-molecule biochemicals will investigate specimens from unmedicated PD patients that were collected up to 2 years apart. Metabolomic analysis involves measuring hundreds of compounds as to individual changes or overall alterations in metabolic pathways. The biochemical components of CSF and blood will be searched for clues that might correlate to Parkinsonian features and progression of the disease.
Project Description:
Specimens in this study are linked to extensive clinical information that will make it possible to investigate correlations to clinical features and to the rate of PD progression.
The specimens will undergo analysis using ultrahigh-performance liquid chromatography linked to tandem mass spectrometry. These state-of-the art methods will characterize much of the metabolic milieu in both the CSF (which circulates through the brain) and in the blood (which would offer a more practical means for monitoring PD biomarkers in a clinical setting). The results of the assays will be compared to identified compounds using a data registry comprising hundreds of entries. Of special interest will be biochemicals that can be linked to the various mechanisms proposed to be involved with neurodegeneration in PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If successful, one implication of this work could be the development of testing for the early diagnosis of PD or for gauging the impact of a neuroprotective treatment on disease progression. Beyond these practical applications, discovery of PD biomarkers would also be likely to open new research directions into what causes this disorder.
Anticipated Outcome:
We hope to detect disease-specific biochemical changes that might appear both in the CSF and plasma specimens. If so, the individual compounds or a composite biomarker might serve to distinguish PD from controls or from other Parkinsonian disorders. A biomarker that changes over time with increase of Parkinsonian features might serve as a surrogate indicator of disease progression in clinical trials. Biomarkers might also provide insight into the underlying disease process, possibly suggesting therapeutic interventions.
Final Outcome
This project used a state-of-the-art analytical technology (metabolomic analysis) to discover promising biomarkers of Parkinson's disease (PD). It studied specimens obtained by the DATATOP clinical trial. Samples of blood and spinal fluid were collected from unmedicated PD patients on two occasions almost one year apart and linked to ratings of PD severity carried out at the same time. The goal was to detect biochemical correlates of PD severity and progression.
Metabolomics refers to laboratory techniques for profiling the pattern of chemical compounds constituting the metabolic milieu. In human metabolism, approximately 2,500 biochemicals can be found. The assays used in this study simultaneously measured several hundred compounds. Metabolomic analysis also depends on sophisticated statistical methods which, in this study, were used to detect correlations between the patterns of biochemicals and clinical ratings. While the spinal fluid results were not informative, a small group of compounds in the blood specimens correlated strongly with ratings of PD progression and severity. If validated, the findings of this biomarker investigation may lead to a sensitive and highly specific means for using a blood sample biochemical profile to monitor the effects of neuroprotective treatment. The particular compounds found to possess PD biomarker properties also might provide new clues as to the origins of this disease.
June 2014