For a study, the researchers sought to assess FBLN2 expression in MS and EAE lesions to see if the ECM molecule could alter oligodendrocyte maturation and remyelination. The study team discovered elevated levels of FBLN2 in EAE and MS lesions using immunofluorescence confocal microscopy and Imaris 3D rendering. Primary oligodendrocyte progenitor cells (OPC) were used to investigate the role of FBLN2 and its processes. FBLN2 was deleted in astrocytes using the Adeno-Associated Virus (AAV) technology, which coded for CRISPR/Cas9 and FBLN2 guide RNA. FBLN2 levels in lesions were higher in GFAP+ astrocytes, which was consistent with the in vitro outcomes of elevated FBLN2 in activated astrocytes but not macrophages or microglia. In tissue culture, FBLN2 did not affect adhesion. Still, it was a potent inhibitor of future maturation of human or mouse OPCs to oligodendrocytes, which corresponded to cell death in real-time tests. Various signaling inhibitors were utilized to investigate FBLN2-mediated pathways in OPCs. FBLN2 suppression was overcome by blocking the Notch signaling pathway. Then, using AAV directed to infect reactive astrocytes and remove their FBLN2 using CRISPR/Cas9, investigators reduced FBLN2 in EAE lesions. When compared to AAV-control injected animals, FBLN2 deficiency resulted in a greater clinical recovery during EAE, which was accompanied by more Olig2+ oligodendrocyte lineage cells in lesions. FBLN2 was a novel extracellular matrix inhibitor of oligodendrocytes and myelin repair that affects NOTCH signaling, according to the outcomes. In MS, defeating FBLN2 has the potential to improve remyelination and prognosis.