Evaluation of the Metabolomics Profile in Charcot-Marie-Tooth (CMT) Patients: Novel Potential Biomarkers
Federica Murgia1,2, Martina Cadeddu3, Jessica Frau4
1Department of Biomedical Sciences, Clinical Metabolomics Unit, University of Cagliari, 09042 Cagliari, Italy.
Background:
Charcot-Marie-Tooth (CMT) is a group of inherited diseases impairing the peripheral nervous system. CMT originates from genetic variants that affect proteins fundamental for the myelination of peripheral nerves and survival. Moreover, environmental and humoral factors can impact disease development and evolution. Currently, no therapy is available. Metabolomics is an emerging field of biomedical research that enables the development of novel biomarkers for neurodegenerative diseases by targeting metabolic pathways or metabolites. This study aimed to evaluate the metabolomics profile of CMT disease by comparing patients with healthy individuals.
Methods:
A total of 22 CMT patients (CMT) were included in this study and were demographically matched with 26 healthy individuals (C). Serum samples were analyzed through Nuclear Magnetic Resonance spectroscopy, and multivariate and univariate statistical analyses were subsequently applied.
Results:
A supervised model showed a clear separation (R2X = 0.3; R2Y = 0.7; Q2 = 0.4; p-value = 0.0004) between the two classes of subjects, and nine metabolites were found to be significantly different (2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate). The combined ROC curve showed an AUC of 0.94 (CI: 0.9-1). Additional altered metabolic pathways were also identified within the disease context.
Conclusion:
This study represents a promising starting point, demonstrating the efficacy of metabolomics in evaluating CMT patients and identifying novel potential disease biomarkers.
Insights
Metabolomics analysis successfully identified nine distinct metabolites differentiating Charcot-Marie-Tooth (CMT) patients from healthy individuals. This finding highlights metabolomics as a promising tool for developing novel biomarkers for CMT disease.
Area of Science:
- Biomedical Research
- Neuroscience
- Metabolomics
Background:
- Charcot-Marie-Tooth (CMT) is an inherited peripheral nervous system disorder with no current therapies.
- Genetic variants affecting myelination proteins and environmental factors contribute to CMT.
- Metabolomics offers a novel approach to identify biomarkers for neurodegenerative diseases.
Purpose of the Study:
- To evaluate the metabolomic profile of Charcot-Marie-Tooth (CMT) patients.
- To identify potential metabolic biomarkers for CMT disease.
Main Methods:
- Serum samples from 22 CMT patients and 26 healthy controls were analyzed.
- Nuclear Magnetic Resonance (NMR) spectroscopy was employed for metabolic profiling.
- Multivariate and univariate statistical analyses were performed.
Main Results:
- A supervised model clearly distinguished CMT patients from controls (Q² = 0.4, p=0.0004).
- Nine significantly different metabolites were identified: 2-hydroxybutyrate, 3-hydroxybutyrate, 3-methyl-2-oxovalerate, choline, citrate, glutamate, isoleucine, lysine, and methyl succinate.
- A combined ROC curve demonstrated high diagnostic accuracy (AUC = 0.94).
Conclusions:
- Metabolomics is effective in evaluating CMT patients.
- This study identified novel potential biomarkers for CMT disease.
- The findings represent a promising step towards developing diagnostic tools for CMT.
