Remyelination modulators in multiple sclerosis patients

Abstract

Multiple Sclerosis (MS) is a complex autoimmune neuro-inflammatory disorder characterized by persistent MS plaques in the central nervous system. Resolution of MS plaques is dependent on the remyelination competence of surviving oligodendrocytes and surrounding environment. Here, we assessed myelination modulators in a 100 MS patients against 77 healthy controls. Plasma fractions were used for the assessment of insulin growth factor binding protein1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) using a Luminex multiplex assay, whereas neurofilament light chain (NF-L) was assessed with an enzyme-linked immunosorbent assay. Circulating levels of IGFBP1, LCN2 and NF-L were significantly higher in MS patients (p<0.01). Whereas BDNF levels were significantly lower in MS patients (p=0.014). MS Female patients had significantly higher levels of IGFBP1 compared to male MS patients (p=0.006). MS patients treated with fingolimod had higher LCN2 levels compared to those on natalizumab (r=0.25, p=0.03). Higher NF-L levels associated with clinically isolated syndrome's (CIS) conversion into MS (p=0.002). We conclude that low BDNF and high LCN2 and NF-L levels are associated with MS pathogenesis, and high IGFBP1level is a biomarker for female MS only, suggesting different MS progression pathways between the sexes. LCN2 is a candidate predictor of response to natalizumab treatment, and NF-L is a candidate predictor of CIS conversion into MS.