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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- hydroxyl radical measured
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parkinson's disease according to Movement Disorders Society criteria
- •Amyotrophic Lateral Sclerosis according to El escorial criteria
- •Age and sex matched healthy controls
排除标准
- •Severe comorbidities (cancer, other degenerative diseases, hemopathy, inflammatory diseases)
研究组 & 干预措施
Amyotrophic lateral sclerosis
ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment
干预措施: placebo (Drug)
Parkinson's disease
ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment
干预措施: placebo (Drug)
healthy age and sex matched controls
ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment
干预措施: placebo (Drug)
Parkinson's disease
ex vivo analysis of lymphocytes from 30 patients with Parkinson's disease with deferiprone and placebo treatment
干预措施: deferiprone (Drug)
Amyotrophic lateral sclerosis
ex vivo analysis of lymphocytes from 30 patients with Amyotrophic lateral sclerosis with deferiprone and placebo treatment
干预措施: deferiprone (Drug)
healthy age and sex matched controls
ex vivo analysis of lymphocytes from 30 healthy age and sex matched controls with deferiprone and placebo treatment
干预措施: deferiprone (Drug)
结局指标
主要结局
hydroxyl radical measured
时间窗: 12 months
hydroxypethidine probe with Fluorescence-activated cell sorting
次要结局
- adenosine triphosphate production measured by seahorse(12 months)
- oxygen consumption measured by seahorse(12 months)
- free reactive iron (ferrous iron)(12 months)
- lipid peroxidation measured by Fluorescence-activated cell sorting(12 months)