Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease

Assistance Publique Hopitaux De Marseille55 enrolled

Overview

This is a 2-year follow-up study of a cohort of 35 CMT1A patients and 20 healthy volunteers. The main objective is identifying prognostic markers for CMT1A using multi-omics analysis. The study is recruiting subjects between the ages of 10 and 30. The most common inherited neuropathy is Charcot-Marie-Tooth disease type 1A (CMT1A), caused by a duplication of the gene expressing PMP22. CMT1A patients develop symptoms in early childhood with variable progression and there is no established therapy until now. Therapy must start in childhood, before peripheral nerves degenerate. However, we lack easily obtainable biomarkers in early disease stages. In CMT-MODs, we will identify disease and prognostic biomarkers in young CMT1A patients.

The CMT-MODs project aims to conduct a multi-omics analysis (transcriptomics, proteomics, lipidomics) in young patients with early-stage CMT1A. This evaluation should enable the identification of prognostic and change-sensitive biomarkers for use in clinical trials. A large cohort of CMT1A children, adolescents and young adults aged 10-30 years over 12 months applying the novel clinical outcome measures CMT Examination Score/CMT Neuropathy Score Version Version 2 Rasch versions (CMTES-R/CMTNSv2-R), the functional outcome measure CMT-FOM, pCMT-Qol, as well as a nerve conduction study (NCS) and quantitative MRI will be assessed. Blood (and optional skin) samples will be taken and gene expression of the most promising candidates will be identified. This assessment of CMT patients at early disease stages will allow CMT-MODs to establish biomarkers that may serve as a standard readout for disease severity and predict the disease course.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

Interventions

Quantitative neuromuscular MRIOTHER

Quantification of biomarkers as fat fraction, magnetization Transfer Ratio, muscular volume, relaxation time T2

Skin biopsyOTHER

Performed on the arm or index finger, depending on patient age

Clinical scoresOTHER

ONLS, CMTES-R, CMT-Peds, CMT-FOM

Blood testOTHER

10 ml sample

Patient Report Outcomes MeasuresOTHER

pCMT-QoL, EVA, WALK-12, PGI-c, SF-12

Eligibility

Sex: ALLMin age: 10 YearsMax age: 30 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy volunteer or patient who has given consent for participation in the study or, for minors, a healthy volunteer whose two parents have given consent for participation in the study. * Patient with genetically confirmed CMT1A or with a parent whose diagnosis is genetically confirmed * Patient able to walk with or without assistance Exclusion Criteria: * Healthy volunteer with neurological disorders * Healthy volunteer or patient with a contraindication to MRI, * Healthy volunteers or patient under 30 kg * Helathy volunteer on long-term therapy * Patient with other neuromuscular pathologies * Patient in a period of exclusion from another research protocol at the time of signing the consent/non-opposition form * Pregnant or breast-feeding women * Subjects covered by articles L1121-5 to 1121-8 of the French Public Health Code (minors, adults under guardianship or trusteeship, patients deprived of their liberty, pregnant or breast-feeding women) * Subjects who cannot read and understand the French language well enough to be able to give their consent to participate in research

Outcomes

Primary Outcomes

Transcriptomic analysis

RNA seq on blood and skin tissues

Time frame: Between inclusion (month 0) and one year later (month 12)

Proteomic analysis

Label-free quantitative approach on blood and skin tissues

Time frame: Between inclusion (month 0) and one year later (month 12)