MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate

Abstract

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing–remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (β = 0.23; 95% CI: 0.04–0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Exploring miRNAs’ Based Modeling Approach for Predicting PIRA in Multiple Sclerosis: A Comprehensive Analysis

“…Different authors investigated the link between miRNA expression and EDSS in serum. Using a backstep multivariate regression analysis, Casanova et al identified hsa-miR-9-5p as significantly correlated with EDSS change over 24 months, mirroring the timeframe of our research [ 34 ]. Conversely, unlike our approach, they did not construct a multivariate model to derive an optimized score associated with EDSS changes over time.…”

“…Furthermore, with the logistic model being indicated as a possible marker of progression in this study, some of the microRNAs identified and correlated with PIRA and EDSS appear to have specific associations with the pathophysiology of multiple sclerosis based on the literature. Some miRNAs have been recently proposed as biomarkers for RRMS in serum [ 34 ] and extracellular vesicles (EVs) [ 35 , 38 , 39 ]. In the present study, we showed that miRNA expression levels were associated with PIRA.…”

“…NLRP3 inflammasome activity is also critical for the inflammation-based microenvironment following demyelination and is a potential therapeutic target for inflammatory-mediated demyelinating diseases, including MS [ 41 ]. The overexpression of miR-24-3p [ 42 ] and the downregulation of miR-223-3p [ 43 ] have already been shown in RRMS, and the correlation with EDSS has been reported [ 34 , 44 ]. Moreover, Scaroni et al in 2022 found both miR-223-3p and miR-24-3p overexpressed in serum EVs in CI (cognitively impaired) MS patients when compared to CP (cognitively preserved) MS patients [ 38 ].…”

“…Modeling approaches, such as logistic and multilinear regressions are essential in modern medicine for predicting outcomes and understanding complex relationships between variables. These statistical tools enabled researchers using a backstep multivariate regression analysis to identify miRNAs significantly correlated with EDSS changes over time in MS patients [ 33 , 34 , 35 ].…”

Role of microRNAs in Immune Regulation with Translational and Clinical Applications

“…In MS patients treated with glatiramer acetate for 2 years, serum miR-138-5p levels were down-regulated in cases of no evidence of disease activity (NEDA-3), whereas increased levels of miR-126-3p and miR-146a-5p were measured if confirmed disability progression (CDP) developed [167]. Circulating miR-29b-5p and miR-185-5p can be applied as biomarkers of treatment response to IFN-β [168,169].…”