@article{87d8e03a5f004b1f851a1fe6729c6786,
title = "Myelin repair stimulated by CNS-selective thyroid hormone action",
abstract = "Oligodendrocyte processes wrap axons to form neuroprotective myelin sheaths, and damage to myelin in disorders, such as multiple sclerosis (MS), leads to neurodegeneration and disability. There are currently no approved treatments for MS that stimulate myelin repair. During development, thyroid hormone (TH) promotes myelination through enhancing oligodendrocyte differentiation; however, TH itself is unsuitable as a remyelination therapy due to adverse systemic effects. This problem is overcome with selective TH agonists, sobetirome and a CNS-selective prodrug of sobetirome called Sob-AM2. We show here that TH and sobetirome stimulated remyelination in standard gliotoxin models of demyelination. We then utilized a genetic mouse model of demyelination and remyelination, in which we employed motor function tests, histology, and MRI to demonstrate that chronic treatment with sobetirome or Sob-AM2 leads to significant improvement in both clinical signs and remyelination. In contrast, chronic treatment with TH in this model inhibited the endogenous myelin repair and exacerbated disease. These results support the clinical investigation of selective CNS-penetrating TH agonists, but not TH, for myelin repair.",
author = "Hartley, {Meredith D.} and Tania Banerji and Tagge, {Ian J.} and Kirkemo, {Lisa L.} and Priya Chaudhary and Evan Calkins and Danielle Galipeau and Shokat, {Mitra D.} and DeBell, {Margaret J.} and {Van Leuven}, Shelby and Hannah Miller and Gail Marracci and Edvinas Pocius and Tapasree Banerji and Ferrara, {Skylar J.} and Meinig, {J. Matthew} and Ben Emery and Dennis Bourdette and Scanlan, {Thomas S.}",
note = "Funding Information: The research was supported by the NIH (DK52798 to TSS), the National Multiple Sclerosis Society (NMSS; RG 5199A4 and RG-1607-25053 to DB; RG 5106A1/1 to BE), the Race to Erase MS (to DB), the OHSU Laura Fund for Innovation in Multiple Sclerosis (to DB and TSS), and gifts from the Ogg and Hoffman families (to TSS, BE, and DB). MDH received postdoctoral funding from the NIH (2T32DK007680-21) and the NMSS (FG 2023A 1/2) with partial support from the Dave Tomlinson Research Fund. IJT received postdoctoral support from the NMSS (FG-16-7-25259). We would like to thank the following core/shared resource facilities at OHSU: Advanced Light Microscopy Core and Electron Microscopy Core (both supported by the NIH, P30 NS061800), the Knight BioLibrary, Mike Lasarev in the Biostatistics & Design Program for data analysis expertise (partially supported by the NIH, UL1TR002369), and the Advanced Imaging Research Center (partially supported by the NIH [S10 RR027694], the W.M. Keck Foundation, and Oregon Opportunity Fund). This material is the result of work supported with resources and the use of facilities at the VA Portland Health Care System, and the contents of this study do not represent the views of the Department of Veteran Affairs or the United States government. Publisher Copyright: {\textcopyright} 2019 American Society for Clinical Investigation.",
year = "2019",
month = apr,
doi = "10.1172/JCI.INSIGHT.126329",
language = "English (US)",
volume = "4",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "8",
}