Although in the relapsing-remitting phase of MS, remyelination is possible-the typical, secondary phase of MS is marked by a slow expansion of lesions, characterized by chronic macrophage activity at the lesion edge, an inability to remyelinate, and progressive neuronal degradation. However, most patients later transition to the secondary, progressive form of MS (SPMS) which is marked by prolonged CNS inflammation, glial cell death, and subsequent and widespread neurodegeneration. Relapsing-remitting MS (RRMS) can last for decades with repeated cycles of enhanced inflammatory periods followed by resolution and partial recovery. (4) Following demyelination, inflammation may be resolved in some lesions, contributing to remyelination and partial functional recovery in patients. (1) These white matter lesions can then lead to muscular, somatosensory, or neurocognitive disabilities depending on their location in the CNS. (4) Despite disease heterogeneity and an unknown combination of factors influencing etiology, the most prevalent presentation of MS (relapsing-remitting MS) involves days to weeks of enhanced inflammation in regionalized areas of the CNS, causing white matter lesions characterized by myelin loss. (3) Furthermore, a combination of genetic and nongenetic factors such as environment, metabolism, and viral infections are believed to significantly contribute to disease risk. (2) It is primarily diagnosed in adults between the ages of 20–40, and affects more females than males.
(1) MS affects nearly 1 million people in the United States alone, and 2.3 million worldwide. Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the central nervous system (CNS), in which oligodendrocytes (OL), the myelinating glia of the CNS, are attacked by inflammatory cells, resulting in myelin degradation, OL death, axonal dysfunction, and neurodegeneration. As remyelination therapies continue to progress into clinical trials, we consider a dual approach targeting the inflammatory microenvironment and intrinsic remyelination mechanisms to be optimal in aiding MS patients. In this review we discuss the complexities of myelin repair following immune-mediated damage in the CNS, the contribution of animal models of MS in providing insight on OL progression and myelin repair, and current and potential remyelination-centered therapeutic targets. Further there have been new findings highlighting various components of the lesion microenvironment that contribute to myelin repair and restored axonal health. Recent advances have provided a better understanding of remyelination processes, specifically oligodendrocyte lineage cell progression following demyelination. Currently available immune-centered therapies are able to reduce the immune-mediated damage exhibited in MS patients, however, they cannot rescue the eventual failure of remyelination or permanent neuronal damage that occurs as MS progresses. Although much progress has been made in developing immunomodulatory treatments to reduce myelin damage and delay the progression of MS, there is a paucity in treatment options that address the multiple pathophysiological aspects of the disease. Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by a complex lesion microenvironment.
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