DIAGALS: Relation Between Tar DNA Binding Protein(TDP)-43 et Nrf-2 in ALS: a Track to Improve Diagnosis and Prognosis of the Disease

University Hospital, Tours60 enrolled

Overview

In response to oxidative stress, cells activate the Nrf-2 pathway, which induces translation of its target genes and corresponding proteins involved in the antioxidant response. This explains the interest in the Nrf-2 pathway in the pathophysiology of Amyotrophic lateral sclerosis (ALS), supported by the results of several studies and the modulatory effect of TDP-43 on the Nrf-2 pathway. Since both TDP-43 and Nrf-2 proteins are present in the peripheral blood mononuclear cells (PBMC) of ALS patients and may be correlated with disease progression, the investigators wish to explore their relationship and their application in the clinic as potential blood biomarkers for ALS.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 YearsHealthy volunteers:

Medical Language ↔ Plain English

Patients group : Inclusion Criteria: * Men and women ≥ 18 years old * Person affiliated to a French social security scheme or equivalent * ALS diagnosed according to El Escorial criteria * Diagnosis of ALS \< 6 months * Onset of symptoms \< 2 years * Signed informed consent Non-inclusion criteria : * Pregnant or breast-feeding * Treatment with oral or injectable anticoagulants, antiplatelet agents (EXCEPT aspirin at the maximum authorized dosage of 160 mg per day) * Unbalanced diabetes * Long-term corticosteroid therapy * Persons deprived of their liberty by judicial or administrative decision; Persons under legal protection: guardianship or curators * Genetic mutations associated with ALS Control group : Inclusion criteria: * Male or female volunteer aged 18 or over * Person affiliated to a French social security scheme or equivalent * Signed informed consent Non-inclusion criteria : * Pregnant or breast-feeding women * Treatment with oral or injectable anticoagulants, antiplatelet agents (except aspirin at the maximum authorized dosage of 160 mg per day) * Unbalanced diabetes * Long-term corticosteroid therapy * Neurological diseases * Patient under legal protection (safeguard of justice, curators and guardianship), or in a situation of deprivation of liberty * Genetic mutations associated with ALS

Outcomes

Primary Outcomes

Presence of TDP-43 aggregates in PBMC

Peripheral blood samples from ALS patients and controls will be collected at inclusion and at follow-up visits for patients. PBMC isolation and monocyte/lymphocyte enrichment will be performed using a Percoll gradient or magnetic bead separation.

Time frame: Evolution between baseline and 6 month

PBMC accompanied by a protein expression profile under Nrf-2 control

From blood samples, RNA will be extracted from PBMCs and expression of Nrf-2 target genes will be analyzed by flow cytometry.

Time frame: Evolution between baseline and 6 month

Secondary Outcomes

Provide a method for identifying TDP-43 in PBMC bly flow cytometry.

From blood samples, use of antibody fragments that recognize TDP-43 in the cell cytoplasm.

Time frame: At 6 month