Metabolomic Exploration of Dysregulated Lipid Metabolism in MFN2-related CMT2A (MetaDLM_CMT2A)

Metabolomic Exploration of Dysregulated Lipid Metabolism in MFN2-related CMT2A (CMT2A) Linked to Mitofusin 2

Charcot-Marie-Tooth (CMT) disease is the commonest sensitivo-motor inherited peripheral neuropathies with a prevalence of about 10-30 per 100,000. To date, more than 80 genes have been found responsible for CMT. Some of these genes code for mitochondrial proteins such as mitofusin 2 (MFN2).

In the last few years, our laboratory has developed strong expertise in metabolomics. The MetaDLM_CMT2A project proposes to produce metabolomic and lipidomic maps in CMT2A plasma from a cohort of genetically and clinically characterized patients with a national recruitment.

In the perspective of future clinical trials, these biomarkers and the better understanding of lipid metabolism defects in CMT2A would be of major interest in monitoring the evolution of the disease and developing specific therapeutic approaches.

Study Overview

• Status: Completed
• Conditions: Charcot-Marie-Tooth Disease Type 2A
• Intervention / Treatment: Procedure: blood sample

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Maine Et Loire
    • Angers, Maine Et Loire, France, 49933
      • CHU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For all participants :

• Adult person
• Person on an empty stomach at the time of inclusion
• Person who signed the study participation consent form
• Person affiliated or beneficiary of a social security scheme

Patients Charcot-Marie-Tooth :

• Patient with symptoms of Charcot-Marie-Tooth disease on clinical examination clinical examination
• Patient with axonal neuropathy confirmed by an electrophysiological study electrophysiological study with a median nerve conduction velocity > 38 m / s
• Patient with documented pathogenic mutation (class 4 or class 5) in the MFN2 or patient with a variant of uncertain significance, as determined by the laboratory performing the test, if the variant of unknown significance has been found in found in multiple affected individuals in a family and not found in unaffected family members in unaffected family members.

Control subject :

• Each control is matched in age and sex to a case previously included in the study.

Exclusion Criteria:

For all participants :

• Pregnant, breastfeeding or parturient woman
• Person deprived of liberty by judicial or administrative decision
• Person subject to forced psychiatric care
• Person subject to a legal protection measure
• Person unable to give consent

Patients Charcot-Marie-Tooth :

• Patient with a neuropathy other than CMT2A (such as diabetic neuropathy or any other cause of acquired neuropathy) neuropathy or any other cause of acquired neuropathy), medical history of kidney stones kidney stones or cardiovascular risk factors (dyslipidaemia diabetes, severe obesity (BMI >35 kg/m²))
• Patient treated with Idebenone at the time of inclusion. (It is possible to include a patient treated with Idebenone if the treatment was interrupted at least 5 days before)

Control subject :

• Person with neuropathy, medical history of kidney stones or cardiovascular risk factors cardiovascular risk factors (dyslipidaemia, diabetes, severe obesity (BMI >35 kg/m²))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Control subjects	Procedure: blood sample; blood sample
Other: Patients Charcot-Marie-Tooth	Procedure: blood sample; blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the metabolomics and lipidomics of CMT2A patients compared to witnesses using high resolution mass spectrometry	We will compare the metabolomics and lipidomics of CMT2A patients compared to controls using high resolution mass spectrometry, by comparing the presence or not of the metabolites sought thanks to thetechnology developed by the company Biocrates (MxP-Quant-500 kit), allowing testing of 630 polar and lipid metabolites, under conditions close to medical biology.	at enrollment

Collaborators and Investigators

• Sponsor: University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2022
• Primary Completion (Actual): June 10, 2024
• Study Completion (Actual): June 10, 2024

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: 2021-A00834-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No