Research:Remyelination in MS

Chang A et al. Cortical remyelination: A new target for repair therapies in multiple sclerosisAnn Neurol. DOI: 10.1002/ana.23693
Objective Generation and differentiation of new oligodendrocytes in demyelinated white matter is the best described repair process in the adult human brain. However, remyelinating capacity falters with age in patients with multiple sclerosis. (MS). Since demyelination of cerebral cortex is extensive in brains from MS patients, we investigated the capacity of cortical lesions to remyelinate and directly compared the extent of remyelination in lesions that involve cerebral cortex and adjacent subcortical white matter.

Methods Postmortem brain tissue from 22 patients with MS (age 27 to 77 years) and 6 subjects without brain disease were analyzed. Regions of cerebral cortex with reduced myelin were examined for remyelination, oligodendrocyte progenitor cells, reactive astrocytes, and molecules that inhibit remyelination.

Results “New” oligodendrocytes that were actively forming myelin sheaths were identified in 30/42 remyelinated subpial cortical lesions, including lesions from three patients in their 70's. Oligodendrocyte progenitor cells were not decreased in demyelinated or remyelinated cortices when compared to adjacent normal-appearing cortex or controls. In demyelinated lesions involving cortex and adjacent white matter, the cortex showed greater remyelination, more actively remyelinating oligodendrocytes and fewer reactive astrocytes. Astrocytes in the white-matter, but not in cortical portions of these lesions, significantly up-regulate CD44, hyaluronan, and versican, molecules that form complexes that inhibit oligodendrocyte maturation and remyelination.
Interpretation Endogenous remyelination of the cerebral cortex occurs in individuals with MS regardless of disease duration or chronological age of the patient. Cortical remyelination should be considered as a primary outcome measure in future clinical trials testing remyelination 
Following damage to oligodendrocytes the default pathway is repair as shown in animals but this can falter in MS. However this new research shows that remyelination is occurring in the grey matter lesions of MS irrespective of disease duration, so there is not a simple failure to repair with age. Just as occurs in EAE there is not a paucity of oligodendrocyte precursor cells, so again telling us we need to make them mature for repair rather than perhaps transplanting stem cells in,. It appears as we already know that astrocyte scarring can inhibit the remyelinating process, but this is not occurring in the grey matter. Therefore repair of the myelin in the grey matter may be an easier first task that we should be aiming at in trials.

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