Studies of miRNAs in Patients with Demyelinating Pathologies: Insights and Challenges

Abstract

Objectives* Demyelinating diseases are a group of pathologies characterized by damage to the myelin sheath and nerve cells. The myelin sheath plays a critical role in enhancing neural conduction velocity and conserving energy required for the propagation of action potentials. This category encompasses conditions such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, and multifocal neuropathy. Researchers are putting significant effort into identifying biomarkers that would help diagnose diseases more accurately and monitor their progression. Based on recommendations from the authors of previous publications to investigate a larger sample size for data reproducibility, we selected two miRNAs (miR-338-5p, miR-219a-5p, miR-146a-5p, miR-31-5p), which had significant associations with the studied pathologies. MiRNAs are short, non-coding, single-stranded molecules primarily involved in regulating gene expression through the suppression of transcription and translation. Materials and Methods In this study, circulating miR-338-5p and miR-219a-5p were investigated in the blood of 20 MS patients, and miR-146a-5p and miR-31-5p were examined in 12 CIDP and 9 MMN patients. Blood samples were collected into special Tempus blood tubes. RNA was isolated from blood using mirVana™ miRNA Isolation Kit (ThermoFisher Scientific (TFS), USA) and the cDNR synthesis was performed using the TaqMan® Advanced miRNA cDNA Synthesis Kit (TFS, USA). MiRNA expression was detected by using qRT-PCR method and the results were analyzed with ThermoFisher Cloud platform. Results The expression of miR-146a-5p and miR-31-5p in the peripheral venous blood of patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy compared to controls, while a significant difference was seen in serum extracellular vesicles. The analysis of differences in miR-338-5p expression showed that miR-338-5p expression was significantly higher in patients that taking 2nd-line treatment compared to those switched from 1st-line to 2nd-line treatment (p<0.05). Conclusions The results may assist in future studies aimed at evaluating the potential of these miRNA markers as diagnostic biomarkers for demyelinating diseases.