The Extracellular Matrix and Remyelination Strategies in Multiple Sclerosis

Significance Statement

Remyelination therapy for multiple sclerosis (MS) is a rapidly emerging research area despite the fact that only limited success has been achieved so far in clinical trials. The extracellular matrix (ECM) is significantly altered in chronic MS lesions, which is believed to be an important remyelination-inhibiting factor. However, the ECM components have not been specifically targeted in current MS remyelinating trials. Qin et al. (2017) described the role of a major ECM protein, fibronectin, in de/remyelination. Exogenous ganglioside GD1a was demonstrated to overcome the remyelination-inhibiting effects of aggregated fibronectin during later stages of oligodendrocyte maturation. Thus, GD1a could potentially be used as a novel remyelinating compound or as combination therapy in conjunction with other drugs to enhance different stages of remyelination in MS.

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system, characterized by inflammatory demyelination and progressive axonal loss. Demyelination has long been considered as the main pathologic feature of MS. Remyelination usually fails in chronic MS lesions despite the presence of oligodendrocyte precursor cells (OPCs; Kuhlmann et al., 2008). A major focus of current MS treatment is on immunomodulation and relapse control. However, it is increasingly believed that chronic demyelination can cause secondary axonal loss (Nave, 2010), which may lead to disease progression and clinical disability. Therefore, remyelinating therapy has become a rapidly emerging MS research area (Plemel et al., 2017). Some novel remyelinating compounds have been developed and progressed into clinical trials. Most of the remyelination clinical trials included patients with optic neuritis as study subjects, because de/remyelination in the visual pathways is more clinically measureable, which can be determined by the latency of visual evoked potentials (VEPs; You et al., 2011). However, only limited success in VEP latency improvement has been achieved to date in the clinical trials (Cadavid et al., 2017; …