Therapeutic regulation of lncRNA profiles in multiple sclerosis: insights from ocrelizumab and cladribine treatments

Abstract Objectives The roles of long non-coding RNAs (lncRNAs) in the regulation of immune responses and their potential as molecular biomarkers in the treatment of multiple sclerosis (MS) are gaining increasing attention. Methods This study aimed to evaluate time-dependent changes in the expression levels of the lncRNAs GAS5, NEAT1, HOTAIR, and MALAT1 in MS patients undergoing Ocrelizumab or Cladribine treatment. A total of 60 patients with relapsing MS were prospectively enrolled and allocated into two treatment groups: Ocrelizumab (n=30) or Cladribine (n=30). In addition, 30 age- and sex-matched healthy controls (HC) were included for baseline comparison. Peripheral blood samples were collected at 1, 3, and 6 months. Total RNA was isolated, and lncRNA expression levels were quantitatively measured using real-time PCR. Results A significant time-dependent increase in GAS5 expression levels was observed in both treatment groups (p<0.05), while NEAT1, HOTAIR, and MALAT1 expression levels significantly decreased at months 3 and 6 compared with month 1 (p<0.05). Subgroup analyses revealed that Ocrelizumab and Cladribine induced similar temporal trends in lncRNA expression profiles despite their differing immunosuppressive mechanisms. Conclusions This study provides early comparative evidence that Ocrelizumab and Cladribine modulate lncRNA expression levels over time in MS patients. The increase in GAS5 and the decrease in NEAT1, HOTAIR, and MALAT1 may represent a molecular signature of immunosuppressive treatment effects. These findings support the potential of lncRNAs as next-generation biomarkers for monitoring treatment response in MS.