New Therapeutic Strategy in ALS Based on Metabolic Status and Associated Metabolic Pathways.

Study Overview
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Brief Summary
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects central and peripheral motor neurons. None of the clinical trials conducted have been clearly successful and the disease remains incurable, putting patients' vital prognosis at risk in the medium term. An alteration of the basal metabolism leading to hypermetabolism has been described in several articles in the literature. The causes of this hypermetabolism and the precise exploration of the metabolic pathways involved are still poorly understood. The fibroblasts of ALS patients may be the site of some metabolic disturbances in this disease with a hypothetical specific basal metabolic profile. These cells are adapted to different metabolic explorations such as omnic approaches. Superficial skin biopsy followed by fibroblast culture can provide a considerable biobank. This cellular richness will allow us, in ALS patients and their controls, to perform metabolomic and lipidomic approaches, as well as the quantification transcriptomic approach.

Detailed Description
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects central and peripheral motor neurons. None of the clinical trials conducted have been clearly successful and the disease remains incurable, putting patients' vital prognosis at risk in the medium term. An alteration of the basal metabolism leading to hypermetabolism has been described in several articles in the literature. The causes of this hypermetabolism and the precise exploration of the metabolic pathways involved are still poorly understood. The fibroblasts of ALS patients may be the site of some metabolic disturbances in this disease with a hypothetical specific basal metabolic profile. These cells are adapted to different metabolic explorations such as omnic approaches. Superficial skin biopsy followed by fibroblast culture can provide a considerable biobank. This cellular richness will allow us, in ALS patients and their controls, to perform experiments for the quantification of metabolites by metabolic and lipidomic approaches, as well as the quantification of mRNAs and the rate of gene transcription by a transcriptomic approach.

Official Title
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New Therapeutic Strategy in ALS Based on Metabolic Status and Associated Metabolic Pathways.

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Other: Samples
* Other: Indirect calorimetry
* Other: Electrical bioimpedance


Participation Criteria
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Eligibility Criteria
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Case group selection criteria: Inclusion Criteria: Age ≥ 18 years and ≥ 75 years ALS according to the El Escorial criteria Diagnosis of ALS < 6 months Symptoms onset < 2 years Patients affiliated to social security scheme Informed consent signed by the patient Exclusion Criteria: Pregnant or breastfeeding women Contraindication to biopsy Contraindication to local anesthesia Treatment with oral or injectable anticoagulants, antiplatelet (except aspirin) Unbalanced Diabetes Systemic corticosteroid treatment Dermatological diseases of the fibroblast Skin cancer Protection measure for guardianship or curatorship Control group selection criteria: Inclusion Criteria: Age ≥ 18 years and ≥ 75 years No neuronal disease Patients affiliated to social security scheme Informed consent signed by the patient Exclusion Criteria: Pregnant or breastfeeding women Contraindication to biopsy Treatment with oral or injectable anticoagulants, antiplatelet (except aspirin) Unbalanced Diabetes Systemic corticosteroid treatment Dermatological diseases of the fibroblast Skin cancer Protection measure for guardianship or curatorship

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Case group<br>The intervention, specific to the study, is to take samples at baseline on patients with Amyotrophic Lateral Sclerosis | Other: Samples<br>* Blood sample, skin biopsy<br>Other: Indirect calorimetry<br>* Measurement of energy expenditure by indirect calorimetry<br>Other: Electrical bioimpedance<br>* Measurement of electrical bioimpedance<br>|
| Other: Control group<br>The intervention, specific to the study, is to take samples at baseline on patients without neurological disease | Other: Samples<br>* Blood sample, skin biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic signature of fibroblast : concentrations of molecules detected by mass spectrometry | The metabolomic profile of fibroblast represents the combination of the different molecules detected/quantified by mass spectrometry | Baseline | 
| Metabolic signature of blood : concentrations of molecules detected by mass spectrometry | The metabolomic profile of blood represents the combination of the different molecules detected/quantified by mass spectrometry | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression levels of targeted molecules using transcriptomics | Choice of molecules based on results obtained by metabolomics approaches | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, Metabolomics, Transcriptomics, Biomarkers, Fibroblast