Remyelination and Multiple Sclerosis: Therapeutic Approaches and Challenges

Current Neurology and Neuroscience Reports

Volumn 14, Issue 10, 2014, Pages

  Hartley, Meredith D ^a   Altowaijri, Ghadah ^b   Bourdette, Dennis ^b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

Animal models; Demyelination; Multiple sclerosis; Oligodendrocytes; OPC differentiation; Remyelination; Stem cell

Indexed keywords

EID: 84905293605     PISSN: 15284042     EISSN: 15346293     Source Type: Journal    
DOI: 10.1007/s11910-014-0485-1     Document Type: Review

References (51)

1. Munzel EA, Williams A. Promoting remyelination in multiple sclerosis-recent advances. Drugs. 2013;73(18):2017–29. This is an excellent review that provides up-to-date information about research regarding potential therapies targeting remyelination.
2. Keough MB, Yong VW. Remyelination therapy for multiple sclerosis. Neurotherapeutics. 2013;10(1):44–54.
3. Zawadzka M, Rivers LE, Fancy SP, Zhao C, Tripathi R, Jamen F, et al. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell. 2010;6(6):578–90.
4. Chang A, Tourtellotte WW, Rudick R, Trapp BD. Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med. 2002;346(3):165–73.
5. Franklin RJ, Ffrench-Constant C, Edgar JM, Smith KJ. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol. 2012;8(11):624–34.
6. Miller RH, Mi S. Dissecting demyelination. Nat Neurosci. 2007;10(11):1351–4.
7. Fancy SP, Chan JR, Baranzini SE, Franklin RJ, Rowitch DH. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci. 2011;34:21–43.
8. de Castro F, Bribian A. The molecular orchestra of the migration of oligodendrocyte precursors during development. Brain Res Brain Res Rev. 2005;49(2):227–41.
9. Simons M, Trotter J. Wrapping it up: the cell biology of myelination. Curr Opin Neurobiol. 2007;17(5):533–40.
10. Chong SY, Chan JR. Tapping into the glial reservoir: cells committed to remaining uncommitted. J Cell Biol. 2010;188(3):305–12.
11. Dubois-Dalcq M, Williams A, Stadelmann C, Stankoff B, Zalc B, Lubetzki C. From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases. Brain. 2008;131(Pt 7):1686–700.
12. Franklin RJ, Ffrench-Constant C. Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci. 2008;9(11):839–55.
13. Franklin RJ, Gallo V. The translational biology of remyelination: past, present, and future. Glia 2014. doi:10.1002/glia.22622. This review highlights the mechanisms of OPC activation and factors influencing OPC activation and remyelination.
14. Chari DM. Remyelination in multiple sclerosis. Int Rev Neurobiol. 2007;79:589–620.
15. Buchet D, Baron-Van EA. In search of human oligodendroglia for myelin repair. Neurosci Lett. 2009;456(3):112–9.
16. Gudi V, Gingele S, Skripuletz T, Stangel M. Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned. Front Cell Neurosci. 2014;8:73. This recent review provides an in-depth discussion of the cuprizone model of demyelination and a thorough comparison of cuprizone with other important demyelination models.
17. Woodruff RH, Franklin RJ. Demyelination and remyelination of the caudal cerebellar peduncle of adult rats following stereotaxic injections of lysolecithin, ethidium bromide, and complement/anti-galactocerebroside: a comparative study. Glia. 1999;25(3):216–28.
18. Hall SM. The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci. 1972;10(2):535–46.
19. Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, et al. A regenerative approach to the treatment of multiple sclerosis. Nature. 2013;502(7471):327–32. This recent paper uses a high-throughput screening approach to identify benztropine, an orally available approved drug, as a therapeutic candidate for promoting myelin repair.
20. Chen Y, Balasubramaniyan V, Peng J, Hurlock EC, Tallquist M, Li J, et al. Isolation and culture of rat and mouse oligodendrocyte precursor cells. Nat Protoc. 2007;2(5):1044–51.
21. Kang SM, Cho MS, Seo H, Yoon CJ, Oh SK, Choi YM, et al. Efficient induction of oligodendrocytes from human embryonic stem cells. Stem Cells. 2007;25(2):419–24.
22. Najm FJ, Lager AM, Zaremba A, Wyatt K, Caprariello AV, Factor DC, et al. Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat Biotechnol. 2013;31(5):426–33.
23. Franklin RJ, Hinks GL. Understanding CNS remyelination: clues from developmental and regeneration biology. J Neurosci Res. 1999;58(2):207–13.
24. Huang JK, Fancy SP, Zhao C, Rowitch DH, Ffrench-Constant C, Franklin RJ. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells. Neurotherapeutics. 2011;8(4):650–8.
25. Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic. CNS Drugs. 2013;27(7):493–503.
26. Goldschmidt T, Antel J, Konig FB, Bruck W, Kuhlmann T. Remyelination capacity of the MS brain decreases with disease chronicity. Neurology. 2009;72(22):1914–21.
27. Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, et al. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006;129(Pt 12):3165–72.
28. Kuhlmann T, Miron V, Cui Q, Wegner C, Antel J, Bruck W. Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain. 2008;131(Pt 7):1749–58.
29. Nave KA. Myelination and support of axonal integrity by glia. Nature. 2010;468(7321):244–52.
30. Su KG, Banker G, Bourdette D, Forte M. Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci Rep. 2009;9(5):411–7.
31. Chou RH, Lu CY, Fan JR, Yu YL, Shyu WC. The potential therapeutic applications of olfactory ensheathing cells in regenerative medicine. Cell Transplant. 2014;23(4):567–71.
32. Williams A. Central nervous system regeneration—where are we? QJM. 2014;107(5):335–9.
33. Jubelt B, Goldman S, Goodman A, Weinstock-Guttman B. Oligodendrocyte progenitor cell delivery for restoration of function in multiple sclerosis: development of a New York Consortium for the Treatment of Myelin Disease. NYSTEM. 2014. Available at: http://stemcell.ny.gov/nystem-consortia-to-accelerate-therapeutic-applications-of-stem-cells.
34. Pirko I, Ciric B, Gamez J, Bieber AJ, Warrington AE, Johnson AJ, et al. A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virus-induced murine model of MS. FASEB J. 2004;18(13):1577–9.
35. Bieber AJ, Warrington A, Asakura K, Ciric B, Kaveri SV, Pease LR, et al. Human antibodies accelerate the rate of remyelination following lysolecithin-induced demyelination in mice. Glia. 2002;37(3):241–9.
36. Calza L, Fernandez M, Giardino L. Cellular approaches to central nervous system remyelination stimulation: thyroid hormone to promote myelin repair via endogenous stem and precursor cells. J Mol Endocrinol. 2010;44(1):13–23.
37. Schumacher M, Hussain R, Gago N, Oudinet JP, Mattern C, Ghoumari AM. Progesterone synthesis in the nervous system: implications for myelination and myelin repair. Front Neurosci. 2012;6:10.
38. Scanlan TS. Sobetirome: a case history of bench-to-clinic drug discovery and development. Heart Fail Rev. 2010;15(2):177–82.
39. Rodriguez-Pena A. Oligodendrocyte development and thyroid hormone. J Neurobiol. 1999;40(4):497–512.
40. Harsan LA, Steibel J, Zaremba A, Agin A, Sapin R, Poulet P, et al. Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis induction and assessment by diffusion tensor magnetic resonance imaging. J Neurosci. 2008;28(52):14189–201.
41. D'Intino G, Lorenzini L, Fernandez M, Taglioni A, Perretta G, Del Vecchio G, et al. Triiodothyronine administration ameliorates the demyelination/remyelination ratio in a non-human primate model of multiple sclerosis by correcting tissue hypothyroidism. J Neuroendocrinol. 2011;23(9):778–90.
42. Hussain R, El-Etr M, Gaci O, Rakotomamonjy J, Macklin WB, Kumar N, et al. Progesterone and nestorone facilitate axon remyelination: a role for progesterone receptors. Endocrinology. 2011;152(10):3820–31.
43. Hussain R, Ghoumari AM, Bielecki B, Steibel J, Boehm N, Liere P, et al. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain. 2013;136(Pt 1):132–46.
44. Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007;64(5):683–8.
45. Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation. 2008;5:32.
46. Huang JK, Jarjour AA, Nait Oumesmar B, Kerninon C, Williams A, Krezel W, et al. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci. 2011;14(1):45–53. This article identifies a specific role for RXR-gamma in accelerating CNS remyelination suggesting that RXR-gamma agonists may represent promising new therapies for myelin repair.
47. Lee S, Chong SY, Tuck SJ, Corey JM, Chan JR. A rapid and reproducible assay for modeling myelination by oligodendrocytes using engineered nanofibers. Nat Protoc. 2013;8(4):771–82.
48. Mi S, Hu B, Hahm K, Luo Y, Kam Hui ES, Yuan Q, et al. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat Med. 2007;13(10):1228–33.
49. Tran J, Palaparthy R, Zhao J, Brosofsky K, Ray S, Rana J, et al. Safety, tolerability and pharmacokinetics of the Anti-LINGO-1 Monoclonal antibody BIIB033 in healthy volunteers and subjects with multiple sclerosis (P02.021). Amer Acad Neurol; April 24, 2012; New Orleans: Neurology.
50. Back SA, Tuohy TM, Chen H, Wallingford N, Craig A, Struve J, et al. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med. 2005;11(9):966–72.
51. Preston M, Gong X, Su W, Matsumoto SG, Banine F, Winkler C, et al. Digestion products of the PH20 hyaluronidase inhibit remyelination. Ann Neurol. 2013;73(2):266–80. This research article identified a new target for myelin repair, PH20, which is a specific hyaluronidase responsible for producing the hyaluronan digestion products that inhibit remyelination in lesions.