Amyotrophic Lateral Sclerosis
Conditions
Brief summary
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.
Interventions
BIOLOGICALBlood sample
The intervention is to take a blood sample every 6 months for 1 year which is not part of health routine care
Sponsors
University Hospital, Tours
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of TDP-43 aggregates in PBMC | Evolution between baseline and 6 month | 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. |
| PBMC accompanied by a protein expression profile under Nrf-2 control | Evolution between baseline and 6 month | From blood samples, RNA will be extracted from PBMCs and expression of Nrf-2 target genes will be analyzed by flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Provide a method for identifying TDP-43 in PBMC bly flow cytometry. | At 6 month | From blood samples, use of antibody fragments that recognize TDP-43 in the cell cytoplasm. |
Contacts
Primary ContactElodie Mousset
Outcome results
None listed