Abstract
Introduction
About 90% of cases of Parkinson’s disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment.
Objective
The aim of our case–control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment.
Methods
We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression.
Results
This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment.
Conclusion
Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are grateful to prof. Steven Symes who supported the linguistic revision of the paper. The study was supported by “Fondazione Grigioni per il Morbo di Parkinson”.
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JT, AL, PB and MA conceived the study. JT and AL wrote the first draft of the manuscript. MA and PB reviewed and critiqued the drafts. JT conceived and performed statistical analysis. CV, KL, MS, AC, MCS and MA recruited the patients and performed the clinical evaluation. All the authors read, critiqued and approved the final version of the manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the local ethics committee and a written consent form was signed by each participant.
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Troisi, J., Landolfi, A., Vitale, C. et al. A metabolomic signature of treated and drug-naïve patients with Parkinson’s disease: a pilot study. Metabolomics 15, 90 (2019). https://doi.org/10.1007/s11306-019-1554-x
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DOI: https://doi.org/10.1007/s11306-019-1554-x