Remyelinating axons

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Science  12 Apr 2019:
Vol. 364, Issue 6436, pp. 142
DOI: 10.1126/science.364.6436.142-c

The search for therapeutic targets to support remyelination in demyelinating diseases such as multiple sclerosis is challenging. Existing oligodendrocytes in the brain do not remyelinate demyelinated axons. Selective estrogen receptor modulators have been suggested to make oligodendrocyte precursor cells (OPCs) differentiate into functional, myelinating cells. In the search for myelinization-promoting agents, Rankin et al. selected bazedoxifene from a high-throughput screen and tested it in vitro and in vivo. This drug increased the differentiation of OPCs into functional oligodendrocytes (both in murine and human cells) and did so when axons were demyelinated after an induced lesion. A genetic knockout experiment revealed that the mechanism of action is independent of its presumed target, the estrogen receptor. Bazedoxifene is already approved by the Food and Drug Administration (as it is regularly prescribed for vasomotor menopausal symptoms in women) and is known for having relatively few side effects, which makes it a promising therapeutic drug for multiple sclerosis.

J. Neurosci. 39, 2184 (2019).

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