CSF MIR-124-3P LINKS DISEASE PROGRESSION, NEURONAL DAMAGE AND SEX DIFFERENCES IN MULTIPLE SCLEROSIS

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. Among them, microRNA-124-3p (miR-124-3p) is highly enriched in the central nervous system, and its dysregulation has been implicated in several neurological disorders, including multiple sclerosis (MS).
Based on bioinformatic analyses performed using the Genome Browser and MIENTURNET, which indicated that miR-124-3p both regulates and is regulated by key neuronal and neuroinflammatory factors, we conducted a retrospective study in a cohort of MS patients to assess its potential as a biomarker of autoimmune-mediated neuronal damage.
MiR-124-3p expression were quantified by LNA-based qPCR in cerebrospinal fluid (CSF) collected at diagnosis. Higher miR-124-3p levels were observed in progressive forms (PMS) compared to those with relapsing–remitting MS (RRMS). Notably, male patients, who typically experience a less frequent but more severe disease course, showed increased miR-124-3p CSF levels compared to females. In addition, Magnetic Resonance Imaging (MRI) analyses revealed, only in males, a positive correlation between CSF miR-124-3p levels and the number of brain lesions.
Moreover, even when CSF miR-124-3p levels were comparable between sexes, male patients exhibited worse performance on both the Timed 25-Foot Walk (T25FW) and the dominant-hand 9-Hole Peg Test (9HPT-DH), which assess lower- and upper-limb function, respectively.
Overall, these findings suggest a potential association between elevated miR-124-3p levels and neuroaxonal damage in MS, supporting the presence of sex-specific protective or compensatory mechanisms in females.
Further studies are ongoing to clarify the underlying mechanisms.