Inflammation in multiple sclerosis: consequences for remyelination and disease progression

Despite the large number of immunomodulatory or immunosuppressive treatments available to treat relapsing-remitting multiple sclerosis (MS), treatment of the progressive phase of the disease has not yet been achieved. This lack of successful treatment approaches is caused by our poor understanding of the mechanisms driving disease progression. Emerging concepts suggest that a combination of persisting focal and diffuse inflammation within the CNS and a gradual failure of compensatory mechanisms, including remyelination, result in disease progression. Therefore, promotion of remyelination presents a promising intervention approach. However, despite our increasing knowledge regarding the cellular and molecular mechanisms regulating remyelination in animal models, therapeutic increases in remyelination remain an unmet need in MS, which suggests that mechanisms of remyelination and remyelination failure differ fundamentally between humans and demyelinating animal models. New and emerging technologies now allow us to investigate the cellular and molecular mechanisms underlying remyelination failure in human tissue samples in an unprecedented way. The aim of this Review is to summarize our current knowledge regarding mechanisms of remyelination and remyelination failure in MS and in animal models of the disease, identify open questions, challenge existing concepts, and discuss strategies to overcome the translational roadblock in the field of remyelination-promoting therapies. Here, the authors summarize current knowledge regarding mechanisms of remyelination and remyelination failure in multiple sclerosis and animal models of the disease and discuss strategies to overcome the translational roadblock in the field of remyelination-promoting therapies.

Automated summary

Despite the availability of immunomodulatory treatments for relapsing-remitting multiple sclerosis (MS), successful treatment of the progressive phase of the disease has not yet been achieved due to limited understanding of disease progression mechanisms. The review summarizes current knowledge on mechanisms of remyelination and failure in MS and animal models, highlighting the need to overcome translation barriers in developing remyelination-promoting therapies.