Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE

Chaudhary, P.; Marracci, G. H.; Calkins, E.; Pocius, E.; Bensen, A. L.; Scanlan, T. S.; Emery, B.; Bourdette, D. N.

doi:10.1101/2020.12.20.423638

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bioRxiv · 10.1101/2020.12.20.423638

Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE

Chaudhary, P.·Marracci, G. H.·Calkins, E.·Pocius, E.·Bensen, A. L.·Scanlan, T. S.·Emery, B.·Bourdette, D. N.

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Abstract

We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4mg/kg), Sob (5mg/kg) or Sob-AM2 (5mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis. HighlightsO_LIThyroid hormone, the thyromimetic Sob and its CNS penetrating prodrug, Sob-AM2, reduce disease severity, reduce myelin and axonal degeneration and protect oligodendrocytes in EAE. C_LIO_LIThe benefits of Sob and Sob-AM2 may be via direct protective effects on oligodendrocytes and reduction in activity of microglia/macrophages. C_LI

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Chaudhary, P., Marracci, G. H., Calkins, E., Pocius, E., Bensen, A. L., Scanlan, T. S., Emery, B., Bourdette, D. N.. 2020-12-21. Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE. https://doi.org/10.1101/2020.12.20.423638

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