Plasma microRNA Signature as Predictive Marker of Clinical Response to Therapy During Multiple Sclerosis.

OBJECTIVE

Despite the availability of effective therapies for Multiple Sclerosis (MS), the unpredictable nature of disease progression and the variability in individual treatment outcomes call for reliable biomarkers. This pilot study aims to investigate the potential of plasma circulating microRNAs (miRNAs) as predictive biomarkers for clinical responses to dimethyl fumarate (DMF), a widely used oral treatment for MS.

METHODS

Peripheral blood samples were collected from nineteen treatment-naïve people with relapsing-remitting MS (pwRRMS) before and after 3, 6, 12, and 24 months of DMF administration, as well as from nineteen healthy individuals. MiRNAs were quantified by RT-qPCR after plasma RNA extraction, and peripheral blood immune cells were analyzed by flow cytometry. Pathway enrichment and protein-protein interaction analyses were performed to identify the biological processes and molecular networks associated with mRNAs targeted by the specific DMF-modulated miRNAs.

RESULTS

We identified a DMF-modulated miRNA signature with significant changes occurring at early treatment stages. Notably, specific miRNAs were correlated with both clinical and immunological outcomes upon DMF treatment, including lymphocyte count reduction (let-7b-5p and miR-223-3p) and disease progression over 2 years (miR-223-3p, miR-23a-3p, miR-23b-3p, miR-27a-3p, and miR-27b-3p), suggesting their potential as predictive biomarkers for treatment response. Moreover, the validated mRNA targets of DMF-modulated miRNAs were enriched for IL-6 signaling and NRF2-dependent antioxidant pathways, highlighting the potential molecular mechanisms underpinning DMF efficacy.

INTERPRETATION

This small exploratory study underscores the potential of plasma circulating miRNAs as candidate biomarkers for predicting therapeutic outcomes in MS and it calls for validation in larger studies, which may enhance our understanding of disease pathophysiology and offer a promising tool for personalized treatment strategies.