Biomarkers of Synaptic Damage in Multiple Sclerosis

Study Overview
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Brief Summary
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A prospective and retrospective cohort study of about five years will be performed on blood and cerebrospinal fluid samples taken for diagnostic reasons from recruited patients within the Neuromed Neurology Unit. Subjects with other chronic neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), and healthy subjects subjected to blood sampling and / or lumbar puncture for clinical reasons will be recruited As control groups.

Detailed Description
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Blood and cerebrospinal fluid samples will be subjected to the procedures required for the isolation of the different components immediately after the withdrawal. Subsequently, the levels of microRNAs, cytokines, chemokines, cell growth factors, neuronal damage markers (tau, phosphorylated and truncated tau, neurofilaments) and mitochondrial (lactate) and free d-amino acids (Objective 1) will be determined. Furthermore, synaptic alterations will be evaluated in the ex vivo chimeric model of MS, using the patch-clamp technique (Objective 2). Genotyping studies will be conducted in order to identify single nucleotide polymorphisms (SNPs) in coding and / or regulating regions of genes (microRNAs or proteins) involved in alterations of the synaptic transmission of MS and its murine experimental model (i.e. SLC1A3, NGFB, PDGFA, etc.), which correlate with specific clinical parameters (i.e. EDSS, BREMS, disease progression index, MS type, disease activity, etc.) and with the levels of potential biomarkers identified

Official Title
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Identification of New Biomarkers Useful to Define the Course of Multiple Sclerosis and Study of the Mechanisms That Promote Synaptic Damage

Conditions
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Multiple Sclerosis, Parkinson Disease, Amyotrophic Lateral Sclerosis, Alzheimer Disease

Intervention / Treatment
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* Procedure: lumbar puncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients (age between 18 and 65 years) Diagnosis of MS in accordance with McDonald's (2010 rev) criteria, EDSS between 0 and 5.5 (included), Patients able to provide informed consent to participation in the study Exclusion Criteria: Inability to provide informed written consent Altered basal blood count Pregnancy or lactation Contraindications for the execution of magnetic resonance imaging with gadolinium Significant clinical conditions in addition to SM or other chronic neurodegenerative diseases including latent viral infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| multiple sclerosis patients<br>lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis | Procedure: lumbar puncture<br>* lumbar puncture performed to detect OCB for diagnostic purposes<br>|
| neurodegenerative disease patients<br>lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis | Procedure: lumbar puncture<br>* lumbar puncture performed to detect OCB for diagnostic purposes<br>|
| control subjects<br>lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis | Procedure: lumbar puncture<br>* lumbar puncture performed to detect OCB for diagnostic purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of predictive biomarkers of SM using an ex vivo chimeric model | CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs | September 01 2020 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of new therapeutic targets in MS. | CSF concentrations of: neurofilaments, beta amyloid, tau protein, inflammatory cytokines and microRNAs | September 01 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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synaptic plasticity, neuroinflammation, neurodegeneration