NEUROKINASE : Expression Profile of ERK5 and PKM2 Kinases in Neuroinflammatory Diseases.
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 主要终点
- Expression of genes encoding ERK5 and PKM2 kinases by RT-qPCR
研究概览
简要总结
Demyelinating diseases represent a broad spectrum of disorders and are induced by excessive inflammation most often triggered by an autoimmune mechanism. Some of these pathologies are chronic and affect the central nervous system such as multiple sclerosis (MS), others are monophasic and target the peripheral nervous system such as Guillain Barré syndrome (GBS).
In neuroinflammatory pathologies, the excessive response of the pro-inflammatory Th1 and Th17 lymphocyte lines and the insufficient response of regulatory T lymphocytes (Treg) cause excessive inflammation which is deleterious to the nervous tissue. The regulation of these signaling pathways involves key proteins such as kinases. Modulation of these kinases which could allow the development of new pharmacological targets for neuroinflammation.
Recent work (unpublished data) has shown an association between the expression of ERK5 and PMK2 kinases, and the clinical severity of experimental allergic encephalomyelitis, a mouse model that mimics multiple sclerosis.
In order to search for new biomarkers and improve our knowledge of the actors of the initial inflammatory phase of neuroinflammatory pathologies, we propose to study the differences in expression of ERK5 and PKM2 kinases in the blood and cerebral spinal fluid (CSF) of patients followed for relapsing-remitting MS and GBS by both RT-qPCR and protein quantification. We also want to study other biological parameters which include characterization of the pro / anti-inflammatory balance by cytokine assay and lymphocyte phenotyping, metabolome study, and mild form neurofilament (NfL) assay.
详细描述
The study of the expression of ERK5 and PKM2 kinases in patients followed for RR MS or GBS, at the beginning of the pathology, will be evaluate.
The usual diagnostic workup for MS and GBS will be performed in order to classify patients into 4 groups :
• Group 1 : control group. Patients that do not fulfill the criteria for MS or GBS and in whom no differential diagnosis was made.
Subgroups 1a and 1b will be formed by respective pairing with groups 2 and 3.
- Group 2 : patients with RR MS confirmed by Macdonald criteria (2017)
- Group 3 : patients with GBS confirmed by the association of the usual clinical and electrophysiological signs.
- Group 4 : patients in whom a differential diagnosis has been identified to explain the symptoms. These patients will be excluded from the analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- 否
入选标准
- •Man and Woman
- •18 to 80 years old
- •Clinical signs that suggest MS or GBS within a month of onset symptom
排除标准
- •Patient treated with immunosuppressive therapy, immunomodulator, or corticosteroids in chronic treatment
- •Patient treated with corticosteroids in the past month
- •without social security
- •HIV positive serology
- •pregnant or breastfeeding woman
- •previous participation in the study
- •under judicial protection
- •non-cooperating patient
结局指标
主要结局
Expression of genes encoding ERK5 and PKM2 kinases by RT-qPCR
时间窗: Day 0
The expression of ERK5 and PKM2 by RT-qPCR will be analyze to investigate the transcriptome on RNA level. RT-qPCR require RNA extraction, reverse transcription into cDNA and then amplification of the genes encoding ERK5 and PKM2 using specific primers designed beforehand. The results will be compared with those obtained with primers of the HPRT gene. These analyzes are carried out using lymphocytes and neutrophils isolated from the blood sample.
次要结局
- Lymphocyte phenotyping(Day 0)
- Metabolome analysis(Day 0)
- Cytokine levels(Day 0)
- Measure of the neurofilament light chain (NfL)(Day 0)