Biomarkers of Synaptic Damage in Multiple Sclerosis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Parkinson Disease; Amyotrophic Lateral Sclerosis; Alzheimer Disease
• Intervention / Treatment: Procedure: lumbar puncture

Detailed Description

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

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• Italy
  • Isernia
    • Pozzilli, Isernia, Italy, 86077
      • Recruiting
      • IRCCS Neuromed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients recruited within the Neurology Unit, IRCCS Neuromed. 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 group.

Description

Inclusion Criteria:

1. Male and female patients (age between 18 and 65 years)
2. Diagnosis of MS in accordance with McDonald's (2010 rev) criteria,
3. EDSS between 0 and 5.5 (included),
4. Patients able to provide informed consent to participation in the study

Exclusion Criteria:

1. Inability to provide informed written consent
2. Altered basal blood count
3. Pregnancy or lactation
4. Contraindications for the execution of magnetic resonance imaging with gadolinium
5. Significant clinical conditions in addition to SM or other chronic neurodegenerative diseases including latent viral infections

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
multiple sclerosis patients; lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture; lumbar puncture performed to detect OCB for diagnostic purposes
neurodegenerative disease patients; lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture; lumbar puncture performed to detect OCB for diagnostic purposes
control subjects; lumbar puncture, microRNAs quantification in blood and CSF samples, SNPs analysis	Procedure: lumbar puncture; lumbar puncture performed to detect OCB for diagnostic purposes

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neuromed IRCCS
• Collaborators: IRCCS Multimedica

Publications and helpful links

General Publications

• Mandolesi G, Rizzo FR, Balletta S, Stampanoni Bassi M, Gilio L, Guadalupi L, Nencini M, Moscatelli A, Ryan CP, Licursi V, Dolcetti E, Musella A, Gentile A, Fresegna D, Bullitta S, Caioli S, Vanni V, Sanna K, Bruno A, Buttari F, Castelli C, Presutti C, De Santa F, Finardi A, Furlan R, Centonze D, De Vito F. The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis. Cells. 2021 Feb 5;10(2):330. doi: 10.3390/cells10020330.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2017
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): September 30, 2027

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: neurodegeneration; synaptic plasticity; neuroinflammation
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurocognitive Disorders; Neuromuscular Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Tauopathies; Multiple Sclerosis; Sclerosis; Parkinson Disease; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Alzheimer Disease
• Other Study ID Numbers: IRCCS Neuromed

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No