Myelin repair stimulated by CNS-selective thyroid hormone action

• DOI: 10.1172/jci.insight.126329
• Publication Date: 2019-04-17T15:09:08Z
• Authors: Meredith D. Hartley; Tania Banerji; Ian J. Tagge; Lisa L. Kirkemo; Priya Chaudhary; Evan Calkins; Danielle Galipeau; Mitra D. Shokat; Margaret J. DeBell; Shelby Van Leuven; Hannah Miller; Gail Marracci; Edvinas Pocius; Tapasree Banerji; Skylar J. Ferrara; J. Matthew Meinig; Ben Emery; Dennis Bourdette; Thomas S. Scanlan
• Keywords: Remyelination

Oligodendrocyte processes wrap axons to form neuroprotective myelin sheaths, and damage in disorders, such as multiple sclerosis (MS), leads neurodegeneration disability. There are currently no approved treatments for MS that stimulate repair. During development, thyroid hormone (TH) promotes myelination through enhancing oligodendrocyte differentiation; however, TH itself is unsuitable a remyelination therapy due adverse systemic effects. This problem overcome with selective agonists, sobetirome CNS-selective prodrug of called Sob-AM2. We show here stimulated standard gliotoxin models demyelination. then utilized genetic mouse model demyelination remyelination, which we employed motor function tests, histology, MRI demonstrate chronic treatment or Sob-AM2 significant improvement both clinical signs remyelination. In contrast, this inhibited the endogenous repair exacerbated disease. These results support investigation CNS-penetrating but not TH,