Oxidative Stress and Apoptosis of Energy Metabolism by Deferiprone From the Circulating Lymphocytes

Study Overview
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Brief Summary
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Peripheral blood mononuclear cells (PBMC) and platelets could be interesting ex vivo models to study brain diseases. Indeed, there is no access to neurons from patients. However, PBMC can exhibit different physiopathological mechanisms that are ubiquitous (i.e. oxidative stress, mitochondriopathy with energy metabolism, inflammation, protein folding, iron metabolism and programmed cell death ...). The platelets are pivotal in the healing system with large range of growth factors. A new therapeutic concept of conservative iron chelation with deferiprone for neuroprotection is under development. The action of deferiprone on the different mechanisms and notably the oxidative stress are to obtain from a collection of PBMC and platelets from patient having Parkinson's disease and Amyotrophic lateral sclerosis and healthy controls to study ex vivo. PBMC and platelets will be stored for future analyses.

Detailed Description
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The study collection of PBMC and platelets from 30 patient having Parkinson's disease 30 patients having Amyotrophic lateral sclerosis and 30 healthy controls. The collection will be performed either by cytapheresis for half of the patient and by collecting the whole blood for the other half. PBMC and platelets will be stored at minus 80°C. PBMC of patients and controls are exposed ex vivo to different pathological condition (mainly Hydrogen peroxide, menadione, hypoxia...) with and without deferiprone to analyse whether the level of oxidative stress (Reactive Oxygen Species and notably hydroxyl radical with hydroxypethidine probe with flow cytometry) is reduced under deferiprone (primary criterion. Secondary analyses will concern the level of iron, the energy metabolism (aerobic versus anaerobic and the level of Adenosine triphosphate production), the type of cell death (apoptosis, autophagy and new programmed cell death: Ferroptosis) and inflammation. Finally, the level of growth factors and their effectiveness will be studied from platelets.

Official Title
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Modulation of Oxidative Stress and Apoptosis of Energy Metabolism by Deferiprone From the Circulating Lymphocytes of Patients With Parkinson's Disease or Amyotrophic Lateral Sclerosis

Conditions
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Parkinson's Disease, Amyotrophic Lateral Sclerosis, Oxidative Stress, Iron Overload

Intervention / Treatment
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* Drug: deferiprone
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's disease according to Movement Disorders Society criteria Amyotrophic Lateral Sclerosis according to El escorial criteria Age and sex matched healthy controls Exclusion Criteria: Severe comorbidities (cancer, other degenerative diseases, hemopathy, inflammatory diseases)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Parkinson's disease<br>ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment | Drug: deferiprone<br>* to test the action of deferiprone on lymphocytes from patients and controls ex vivo<br>* Other names: FERRIPROX;Drug: placebo<br>* to control the action of placebo on lymphocytes from patients and controls ex vivo<br>|
| Active Comparator: Amyotrophic lateral sclerosis<br>ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment | Drug: deferiprone<br>* to test the action of deferiprone on lymphocytes from patients and controls ex vivo<br>* Other names: FERRIPROX;Drug: placebo<br>* to control the action of placebo on lymphocytes from patients and controls ex vivo<br>|
| Placebo Comparator: healthy age and sex matched controls<br>ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment | Drug: deferiprone<br>* to test the action of deferiprone on lymphocytes from patients and controls ex vivo<br>* Other names: FERRIPROX;Drug: placebo<br>* to control the action of placebo on lymphocytes from patients and controls ex vivo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hydroxyl radical measured | hydroxypethidine probe with Fluorescence-activated cell sorting | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adenosine triphosphate production measured by seahorse | seahorse experimentation | 12 months | 
| oxygen consumption measured by seahorse | seahorse experimentation | 12 months | 
| free reactive iron (ferrous iron) | calceine assay | 12 months | 
| lipid peroxidation measured by Fluorescence-activated cell sorting | flow cytometry with bodipy probe | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Amyotrophic lateral sclerosis, Peripheral blood mononuclear cells, ex vivo model for oxidative stress, iron metabolism and chelation