The Regulatory Role of miRNA 27 Follistatin Like Protein-1 Gene in Multiple Scelerosis

February 29, 2024 updated by: Rasha Mohammed Ali, Assiut University

The Regulatory Role of miRNA 27 and Follistatin Like Protein-1 Gene in the Pathophysiology of Multiple Sclerosis Patients.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination of the central nervous system. Young women between the ages of 20 and 40 are primarily targeted by this disabling disorder. Till now there are no sufficient mechanisms to explain the pathophysiology of multiple sclerosis.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including multiple sclerosis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain.

Recent researchers have discovered that microRNAs (miRNAs) contribute to the pathophysiology of MS, primarily influencing glial cells and the immune cells in the periphery. In recent years, miRNAs have become more prevalent as inflammation and demyelination process regulators in MS.

miRNAs are naturally occurring, non-coding RNA molecules (21-25 nucleotides). miRNAs play a part in the post-transcriptional regulation of gene expression and silencing of RNA. miRNAs have been discovered to control some physiological processes, as apoptosis, proliferation, differentiation, and development.

Measurement of circulating miRNAs in MS patients' peripheral blood is one of the promising approaches as it can be a non-invasive tool to explain its pathogenesis. miRNAs are remarkably stable in bodily fluids and are relatively simple to collect and quantify. Moreover, a novel approach to therapy may be based on methods that regulate the activity of miRNAs.

Several miRNAs particularly miR-27 have been reportedly involved in regulating myelination in the central nervous system. However, the role of micro RNAs in generation or progression of MS remains elusive.

Follistatin-like protein-1 (FSTL1) was first identified as a transforming growth factor β1-inducible protein. In the last decade, FSTL1 has been identified as a novel inflammatory protein. FSTL1 is a glycoprotein rich in cysteine (SPARC) family. FSTL1 is elevated in various inflammatory conditions and decreased during treatment.

Moreover, a variety of studies suggest that targeting of FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. Recent studies revealed a substantial connection between FSTL1 and micro-RNA 27 levels and demonstrated that the regulatory effects of miR-27 in some inflammatory conditions may be exerted by targeting FSTL1.

This study aims to investigate the expression patterns of miR-27 and Follistatin like 1 gene in peripheral blood samples of MS patients. As, we hypothesize that miR-27 and its target gene (FSTL1) may serve important roles in the pathogenesis of MS.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Study subjects:

  1. Inclusion criteria:

    1. Patients diagnosed with MS based on the revised McDonald criteria.
    2. Female patients will only be included.
    3. 20- 45 years old.
    4. Drug naïve.

  2. Exclusion criteria:

    1. Patients with other neurodegenerative and autoimmune disorders.
    2. Pregnant females.
    3. Co-existing chronic hypertension, diabetes, and epilepsy
    4. Chronic renal or hepatic diseases

Description

Inclusion Criteria:

  1. Patients diagnosed with MS based on the revised McDonald criteria.
  2. Female patients will only be included.
  3. 20- 45 years old.
  4. Drug naïve.

Exclusion Criteria:

  • 1. Patients with other neurodegenerative and autoimmune disorders. 2. Pregnant females. 3. Co-existing chronic hypertension, diabetes, and epilepsy 4. chronic renal or hepatic diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Multiple sclerosis patients (MS)

included 40 patients with newly discovered MS (duration of the disease is 3 years or less) and diagnosed according to the revised McDonald criteria. The patients will be recruited from the neurology department of Assiut University Hospital.

MS patients will be further subdivided into two subgroups: 20 patients with RRMS and 20 patients with Progressive MS group.
Diagnostic test: micro RNA 27- FLP1 gene expression

From each participant, 2 mL of blood will be drawn and store at 25-degree C. The expression of miRNA-27 and FLP1 gene will be measured using real time PCR.

Relative expression values will be normalised to the housekeeping gene GAPDH. The comparative cycle threshold (Ct) approach will be used to measure the relative expression of miRNA 27 and FLP1 gene. Then, using the equation -ΔΔCT, the fold change of each gene will be determined

Diagnostic test: The Expanded Disability Status Scale (EDSS)

The Expanded Disability Status Scale (EDSS) is a way of measuring how much someone is affected by their MS. Neurologists use it to monitor changes in the level of someone's disability over time. The EDSS has a range from 0 to 10.

Zero points is normal neurological examination. 10 points shows the MS-related death cases. Patients with EDSS score up to 5 are fully ambulatory patients.

Diagnostic test: Electrophysiological assessment:
Electromyography and nerve conduction velocity will be performed for all MS patients.
Diagnostic test: MRI examination MRI brain:
will be done on all MS patients to detect the number, the site, and the enhancement of lesions
Control (C)
Group II: included 20 healthy individuals who will be age- and sex-matched as a control group, with no history of any neurological or autoimmune disease.
Diagnostic test: micro RNA 27- FLP1 gene expression

From each participant, 2 mL of blood will be drawn and store at 25-degree C. The expression of miRNA-27 and FLP1 gene will be measured using real time PCR.

Relative expression values will be normalised to the housekeeping gene GAPDH. The comparative cycle threshold (Ct) approach will be used to measure the relative expression of miRNA 27 and FLP1 gene. Then, using the equation -ΔΔCT, the fold change of each gene will be determined

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• To measure the levels of miR-27 expression and its target gene (FSTL1) in progressive MS and relapsing-remitting multiple sclerosis (RRMS) patients.
Time Frame: 1 month
RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To correlate the levels of expression of miR-27 expression and its target gene (FSTL1) relative to the severity of symptoms of MD patients.
Time Frame: 1 month
Statistical analysis: Pearson correlation for parametric data, spearman correlation for non-parametric data.
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

March 1, 2026

Study Registration Dates

First Submitted

February 20, 2024

First Submitted That Met QC Criteria

February 29, 2024

First Posted (Actual)

March 4, 2024

Study Record Updates

Last Update Posted (Actual)

March 4, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOGR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Sclerosis

Clinical Trials on micro RNA 27- FLP1 gene expression

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe