A Metabolomics Approach to Pharmacotherapy Personalization

Balashova, Elena E.; Maslov, Dmitry L.; Lokhov, Petr G.

doi:10.3390/jpm8030028

Cited by 64 publications

(39 citation statements)

References 89 publications

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“…Metabotype information can be used to identify alterations in biochemical pathways in ALS patients that are modified or not by treatment. This new field, called pharmacometabolomics, allows clinicians to identify a metabolic state at baseline and after drug therapy, increasing information about treatment outcomes, especially drug-response phenotype (59).…”

Section: Metabolomics-driven Therapeutics Management: the Advent Of Pmentioning

confidence: 99%

Metabolomics Biomarkers: A Strategy Toward Therapeutics Improvement in ALS

et al. 2018

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Biomarkers research in amyotrophic lateral sclerosis (ALS) holds the promise of improving ALS diagnosis, follow-up of patients, and clinical trials outcomes. Metabolomics have a big impact on biomarkers identification. In this mini-review, we provide the main findings of metabolomics studies in ALS and discuss the most relevant therapeutics attempts that targeted some prominent alterations found in ALS, like glutamate excitotoxicity, oxidative stress, alterations in energetic metabolism, and creatinine levels. Metabolomics studies have reported putative diagnosis or prognosis biomarkers, but discrepancies among these studies did not allow validation of metabolic biomarkers for clinical use in ALS. In this context, we wonder whether metabolomics knowledge could improve ALS therapeutics. As metabolomics identify specific metabolic pathways modified by disease progression and/or treatment, we support that adjuvant or combined treatment should be used to rescue these pathways, creating a new perspective for ALS treatment. Some ongoing clinical trials are already trying to target these pathways. As clinical trials in ALS have been disappointing and considering the heterogeneity of the disease presentation, we support the application of a pharmacometabolomic approach to evaluate the individual response to drug treatments and their side effects, enabling the development of personalized treatments for ALS. We suggest that the best strategy to apply metabolomics for ALS therapeutics progress is to establish a metabolic signature for ALS patients in order to improve the knowledge of patient metabotypes, to choose the most adequate pharmacological treatment, and to follow the drug response and side effects, based on metabolomics biomarkers.

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Section: Metabolomics-driven Therapeutics Management: the Advent Of Pmentioning

confidence: 99%

Metabolomics Biomarkers: A Strategy Toward Therapeutics Improvement in ALS

et al. 2018

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“…In addition, the cellular interactions and exchange of metabolites between the retina, RPE, and choroid complex also provide an important basis of studying local metabolomic alterations in AMD. Considering that the metabolome is closer to the molecular phenotype than either the genome, the transcriptome, or the proteome [16], the study of metabolites could lead to better prediction of the resulting phenotype than other -omics approaches. With AMD progression increasingly associated with metabolic dysfunction, there is the potential for systemic and local metabolic biomarkers to provide opportunities to detect and follow the progression of the disease at an early stage.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics and Age-Related Macular Degeneration

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et al. 2018

Metabolites

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Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution.

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“…Furthermore, the quality of 2D spectra obtained from these instruments in half an hour would broaden the horizon of their potential applications.Metabolites 2020, 10, 155 2 of 13 which also give rise to improved understandings of their pathologies. This, in turn, may also lead to the identification of suitable drug targets [3].Moreover, in addition to pathologies, such approaches may also provide a complete and systematic profiling of metabolites and their temporal changes caused by factors such as diet, lifestyle, environment and administered drugs. This is possible through the multicomponent analysis of body fluids and/or extracts of tissue biopsy samples, coupled with a statistical interpretational strategy known as multivariate analysis [4].…”

mentioning

confidence: 99%

“…Metabolites 2020, 10, 155 2 of 13 which also give rise to improved understandings of their pathologies. This, in turn, may also lead to the identification of suitable drug targets [3].…”

mentioning

confidence: 99%

Benchtop Low-Frequency 60 MHz NMR Analysis of Urine: A Comparative Metabolomics Investigation

et al. 2020

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Metabolomics techniques are now applied in numerous fields, with the ability to provide information concerning a large number of metabolites from a single sample in a short timeframe. Although high-frequency (HF) nuclear magnetic resonance (NMR) analysis represents a common method of choice to perform such studies, few investigations employing low-frequency (LF) NMR spectrometers have yet been published. Herein, we apply and contrast LF and HF 1H-NMR metabolomics approaches to the study of urine samples collected from type 2 diabetic patients (T2D), and apply a comparative investigation with healthy controls. Additionally, we explore the capabilities of LF 1H-1H 2D correlation spectroscopy (COSY) experiments regarding the determination of metabolites, their resolution and associated analyses in human urine samples. T2D samples were readily distinguishable from controls, with several metabolites, particularly glucose, being associated with this distinction. Comparable results were obtained with HF and LF spectrometers. Linear correlation analyses were performed to derive relationships between the intensities of 1D and 2D resonances of several metabolites, and R2 values obtained were able to confirm these, an observation attesting to the validity of employing 2D LF experiments for future applications in metabolomics studies. Our data suggest that LF spectrometers may prove to be easy-to-use, compact and inexpensive tools to perform routine metabolomics analyses in laboratories and ‘point-of-care’ sites. Furthermore, the quality of 2D spectra obtained from these instruments in half an hour would broaden the horizon of their potential applications.

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A Metabolomics Approach to Pharmacotherapy Personalization

Cited by 64 publications

References 89 publications

Metabolomics Biomarkers: A Strategy Toward Therapeutics Improvement in ALS

Metabolomics Biomarkers: A Strategy Toward Therapeutics Improvement in ALS

Metabolomics and Age-Related Macular Degeneration

Benchtop Low-Frequency 60 MHz NMR Analysis of Urine: A Comparative Metabolomics Investigation

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