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Expression Profile of ERK5 and PKM2 Kinases in Neuroinflammatory Diseases. (NEUROKINASE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04674163
Recruitment Status : Not yet recruiting
First Posted : December 19, 2020
Last Update Posted : February 11, 2021
Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM)
Information provided by (Responsible Party):
Centre Hospitalier Régional d'Orléans

Brief Summary:

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Recent work (unpublished data) has shown an association between the expression of ERK5 and PMK2 kinases, and the clinical severity of experimental allergic encephalomyelitis, a mouse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.

Condition or disease Intervention/treatment Phase
Sclerosis, Multiple Guillain-Barre Syndrome Inflammation Biological: Blood sample and Cerebrospinal fluid (CSF) collection. Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: NEUROKINASE : Expression Profile of ERK5 and PKM2 Kinases in Neuroinflammatory Diseases.
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Patients with clinical signs that suggest Multiple Sclerosis (MS) or Guillain Barré Syndrome (GBS) Biological: Blood sample and Cerebrospinal fluid (CSF) collection.
An additional blood sample (25 ml) and a cerebrospinal fluid (CSF) sample (2 ml) will be taken.

Primary Outcome Measures :
  1. Expression of genes encoding ERK5 and PKM2 kinases by RT-qPCR [ Time Frame: 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.

Secondary Outcome Measures :
  1. Lymphocyte phenotyping [ Time Frame: Day 0 ]
    Lymphocyte phenotyping will be performed by flow cytometry from PBMCs. We will use antibodies against Th1, Th2, Th9, Th17, Th22, Treg and TFH populations.

  2. Cytokine levels [ Time Frame: Day 0 ]
    A panel of cytokines, mainly pro-inflammatory, will be studied in plasma and in CSF by ELISA. The panel includes the following cytokines: IL17, TNF, IL6, Il 1β, IL 10, IL33, IL12, IL 23

  3. Metabolome analysis [ Time Frame: Day 0 ]
    Metabolome analyzes will be performed from plasma and CSF. These analyzes will be carried out by liquid chromatography coupled with mass spectrometry (LC-MS) by the Metabohub network (MetaboHUB-Clermont for plasma analyzes and MetaboHUB-Saclay for CSF analyzes).

  4. Measure of the neurofilament light chain (NfL) [ Time Frame: Day 0 ]
    NfL levels in blood and CSF will be studied to determine if there is an increase in NfL levels in patients followed for GBS and to compare the NfL levels of these patients with patients followed for MS.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Man and Woman
  • 18 to 80 years old
  • Clinical signs that suggest MS or GBS within a month of onset symptom

Exclusion Criteria:

  • 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
  • dementia
  • pregnant or breastfeeding woman
  • previous participation in the study
  • under judicial protection
  • non-cooperating patient

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04674163

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Contact: Aurélie DESPUJOLS +33238744071
Contact: Elodie POUGOUE TOUKO +33238744086

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CHR Orléans
Orléans, France, 45067
Contact: Pascal AUZOU, Dr    +33 2 38 22 99 47   
Principal Investigator: Pascal AUZOU, Dr         
Sponsors and Collaborators
Centre Hospitalier Régional d'Orléans
Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM)
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Principal Investigator: Pascal AUZOU, Dr CHR Orléans

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Responsible Party: Centre Hospitalier Régional d'Orléans Identifier: NCT04674163    
Other Study ID Numbers: CHRO-2018-07
First Posted: December 19, 2020    Key Record Dates
Last Update Posted: February 11, 2021
Last Verified: February 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier Régional d'Orléans:
ERK5 kinase
M2 Type Pyruvate Kinase
Additional relevant MeSH terms:
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Guillain-Barre Syndrome
Multiple Sclerosis
Pathologic Processes
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Demyelinating Autoimmune Diseases, CNS