542
Views
8
CrossRef citations to date
0
Altmetric
Review

Glial cells as therapeutic targets in progressive multiple sclerosis

, ORCID Icon & ORCID Icon
Pages 481-494 | Received 08 Feb 2019, Accepted 30 Apr 2019, Published online: 13 May 2019

References

  • Rotstein DL, Chen H, Wilton AS, et al. Temporal trends in multiple sclerosis prevalence and incidence in a large population. Neurology. 2018;90:1535-1441.
  • Dilokthornsakul P, Valuck RJ, Nair KV, et al. Multiple sclerosis prevalence in the United States commercially insured population. Neurology. 2016;86:1014–1021.
  • Gilmour H, Ramage-Morin PL, Wong SL. Multiple sclerosis: prevalence and impact. Heal Reports. 2018;29:3–8.
  • Goldenberg MM. Multiple sclerosis review. Pharmacol Ther. 2012;37:175–184.
  • Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17:162–173.
  • Fred D, Lublin M, Stephen C, et al. Defining the clinical course of multiple sclerosis the 2013 revisions. Neurology. 2014;83:278–286.
  • McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8:913–919.
  • Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Curr Neuropathol. 2011;9:409–416.
  • Lucchinetti CF, Rodriguez M. The controversy surrounding the pathogenesis of the multiple sclerosis lesion. Mayo Clin Proc. 1997;72:665–678.
  • Winger RC, Zamvil SS. Antibodies in multiple sclerosis oligoclonal bands target debris. Proc Natl Acad Sci. 2016;113:7696–7698.
  • Dobson R, Ramagopalan S, Davis A, et al. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013;84:909–914.
  • Loleit V, Biberacher V, Hemmer B. Current and future therapies targeting the immune system in multiple sclerosis. Curr Pharm Biotechnol. 2014;15:276–296.
  • Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14:778–809.
  • Pestka S, Langer JA. Interferons and their actions. Annu Rev Biochem. 1987;5656:727727–777777.
  • Liu Z, Pelfrey CM, Cotleur A, et al. Immunomodulatory effects of interferon beta-1a in multiple sclerosis. J Neuroimmunol. 2001;112:153–162.
  • Burdin N, Van Kooten C, Galibert L, et al. Endogenous IL-6 and IL-10 contribute to the differentiation of CD40-activated human B lymphocytes. J Immunol. 1995;154:2533–2544.
  • de Waal Malefyt R, Abrams J, Bennett B, et al. IL-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by Monocytes. 1991;174:1209-1220.
  • Mayr WT, Pittock SJ, McClelland RL, et al. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985–2000. Neurology. 2003;61:1373–1377.
  • Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Medical progress: multiple sclerosis. N Engl J Med. 2000;343:938–952.
  • Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol. 1996;39:285–294.
  • Paty DW, Li D. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. Neurology. 1993;43:662–667.
  • Durelli L, Verdun E, Barbero P, et al. Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN). Lancet. 2002;359:1453–1460.
  • Fischer JS, Priore RL JL, Jacobs LD, et al. Neuropsychological effects of interferon β-1a in relapsing multiple sclerosis. multiple sclerosis collaborative research group. Ann Neurol. 2000;48:885–892.
  • Goodin D, Frohman E, Hurwitz B, et al. Neutralizing antibodies to interferon beta: assessment of their clinical and radiographic impact: an evidence report. Neurology. 2007;68:977–984.
  • Rudick RA, Ransohoff RM, Lee JC, et al. In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis. Neurology. 1998;50:1294–1300.
  • Neilley LK, Goodin DS, Goodkin DE, et al. Side effect profile of interferon beta-lb in MS: results of an open label trial. Neurology. 1996;46:552–553.
  • Walther EU, Hohlfeld R. Multiple Slecrosis: side effects of interferon beta therapy and their management. Neurology. 1999;53:1622–1627.
  • Goeb JL, Even C, Nicolas G, et al. Psychiatric side effects of interferon-β in multiple sclerosis. Eur Psychiatry. 2006;21:186–193.
  • Neuhaus O, Farina C, Wekerle H, et al. Mechanisms of action of glatiramer. Nuerology. 2001;56:702–708.
  • Gran B, Tranquill L, Chen M, et al. Mechanisms of immunomodulation by glatiramer acetate. Neurology. 2000;55:1704–1714.
  • Ford C, Goodman AD, Johnson K, et al. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate. Mult Scler. 2010;16:342–350.
  • Wolinsky JS, Narayana PA, O’Connor P, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007;61:14–24.
  • Johnson KP, Brooks BR, Cohen JA, et al. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology. 1998;50:701-708.
  • Pöllmann W, Erasmus LP, Feneberg W, et al. Interferon beta but not glatiramer acetate therapy aggravates headaches in MS. Neurology. 2002;59:636–639.
  • Warnke C, Zu Hörste GM, Hartung HP, et al. Review of teriflunomide and its potential in the treatment of multiple sclerosis. Neuropsychiatr Dis Treat. 2009;5:333–340.
  • Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. 2011;124:75–84.
  • O’Connor P, Wolinsky JS, Confavreux C, et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365:1293–1303.
  • Brinkmann V, Billich A, Baumruker T, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010;9:883–897.
  • Suzanne M, Richard H, James B, et al. Alteration of lymphocyte trafficking by sphingosine- 1-phosphate receptor agonists. Science. 2002;296:346–349.
  • Matloubian M, Lo CG, Cinamon G, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427:355–360.
  • Foster CA, Howard LM, Schweitzer A, et al. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther. 2007;323:469–475.
  • Comi G, O’Connor P, Montalban X, et al. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results. Mult Scler. 2010;16:197–207.
  • Khatri B, Barkhof F, Comi G, et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: A randomised extension of the TRANSFORMS study. Lancet Neurol. 2011;10:520–529.
  • Schulze-Topphoff U, Varrin-Doyer M, Pekarek K, et al. Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2. Proc Natl Acad Sci. 2016;113:4777–4782.
  • Albrecht P, Bouchachia I, Goebels N, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012;9:1–10.
  • Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011;134:678–692.
  • Viglietta V, Miller D, Bar-Or A, et al. Efficacy of delayed-release dimethyl fumarate in relapsing-remitting multiple sclerosis: integrated analysis of the phase 3 trials. Ann Clin Transl Neurol. 2015;2:103–118.
  • Yednock T, Cannon C, Fritz L, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin. Nature. 1992;356:63–66.
  • Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2003;348:15–23.
  • Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2004;351:1493–1501.
  • Sorensen PS, Blinkenberg M. The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord. 2016;9:44–52.
  • Kappos L, Li D, Calabresi PA, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: A phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378:1779–1787.
  • Emery P, Rigby W, Tak PP, et al. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS One. 2014;9:8.
  • Smith PJ, Morgan SA, Fox ME, et al. Mitoxantrone-DNA binding and the induction of topoisomerase II associated DNA damage in multi-drug resistant small cell lung cancer cells. Biochem Pharmacol. 1990;40:2069–2078.
  • Fox EJ. Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther. 2006;28:461–474.
  • Olindo S, Gullion B, Helias J, et al. Decrease in heart ventricular ejection fraction during multiple sclerosis. Eur J Neurol. 2002;9:287–291.
  • Senaratne MPJ, Carroll D, Warren KG, et al. Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1984;47:947–952.
  • Flachenecker P, Wolf A, Krauser M, et al. Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance. J Neurol. 1999;246:578–586.
  • Issacs ALJ. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–267.
  • Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. J Fur Neurol Neurochir Psychiatr. 2017;18:30–31.
  • Aloisi F. Immune function of microglia. Glia. 2001;36:165–179.
  • Husemann J, Loike JD, Anankov R, et al. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia. 2002;40:195–205.
  • Graeber MB, Streit WJ. Microglia: biology and pathology. Acta Neuropathol. 2010;119:89–105.
  • Kierdorf K, Prinz M. Factors regulating microglia activation. Front Cell Neurosci. 2013;7:1–8.
  • Chu F, Shi M, Zheng C, et al. The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neuroimmunol. 2018;318:1–7.
  • Wu Y, Dissing-Olesen L, Macvicar BA, et al. Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol. 2016;36:605–613.
  • Luo C. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat. 2017;13:1661–1667.
  • Chastain EML, Duncan DS, Rodgers JM, et al. The role of antigen presenting cells in multiple sclerosis. Biochim Biophys Acta - Mol Basis Dis. 2011;1812:265–274.
  • Kielian T, Mayes P, Kielian M. Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression. J Neuroimmunol. 2002;130:86–99.
  • Gudi V, Gingele S, Skripuletz T, et al. Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned. Front Cell Neurosci. 2014;8:1–24.
  • Neumann H, Kotter MR, Franklin RJM. Debris clearance by microglia: an essential link between degeneration and regeneration. Brain. 2009;132:288–295.
  • Hiremath MM, Saito Y, Knapp GW, et al. Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice. J Neuroimmunol. 1998;92:38–49.
  • Voß EV, Škuljec J, Gudi V, et al. Characterisation of microglia during de- and remyelination: can they create a repair promoting environment? Neurobiol. Dis. 2012;45:519–528.
  • Mason JL, Ye P, Suzuki K, et al. Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. Nat Commun. 2000;20:5703–5708.
  • Pérez-Martín M, Cifuentes M, Grondona JM, et al. IGF-I stimulates neurogenesis in the hypothalamus of adult rats. Eur J Neurosci. 2010;31:1533–1548.
  • McKinnon RD, Matsui T, Dubois-Dalcq M, et al. FGF modulates the PDGF-driven pathway of oligodendrocyte development. Neuron. 1990;5:603–614.
  • Muir DA, Compston DAS. Growth factor stimulation triggers apoptotic cell death in mature oligodendrocytes. J Neurosci Res. 1996;44:1–11.
  • Kumar S, Biancotti J, Yamaguchi M, et al. Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model. Nuerochem Res. 2007;32:783–797.
  • Lodge P, Sriram S. Regulation of microglial activation by TGF‐β, IL‐10, and CSF‐1. J Leukoc Biol Suppl. 1996;60:502–508.
  • Sriram S, Rodriguez M. Indictment of the microglia as the villain in multiple sclerosis. Neurology. 1997;48:464–470.
  • Warrington AE, Asakura K, Bieber AJ, et al. Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis. Pnas. 2000;97:6820–6825.
  • Warrington AE, Bieber AJ, Ciric B, et al. A recombinant human IgM promotes myelin repair after a single, very low dose. J Neurosci. 2007;85:967–976.
  • Mullin AP, Cui C, Wang Y, et al. rHIgM22 enhances remyelination in the brain of the cuprizone mouse model of demyelination. Neurobiol Dis. 2017;105:142–155.
  • Zorina Y, Stricker J, Caggiano AO, et al. Human IgM antibody rHIgM22 promotes phagocytic clearance of myelin debris by microglia. Sci Rep. 2018;8:1–14.
  • Weinstein JR, Quan Y, Hanson JF, et al. IgM-dependent phagocytosis in microglia is mediated by complement receptor 3, not fc/receptor. J Immunol. 2015;195:5309–5317.
  • Airas L, Nylund M, Rissanen E. Evaluation of microglial activation in multiple sclerosis patients using positron emission tomography. Front Neurol. 2018;9:1–10.
  • Politis M, Giannetti P, Su P, et al. Increased PK11195 PET binding in the cortex of patients with MS correlates with disability. Neurology. 2012;79:523–530.
  • Sellebjerg F, Cadavid D, Steiner D, et al. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis. Ther Adv Neurol Disord. 2016;9:31–43.
  • Kapoor R, Ho PR, Campbell N, et al. Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND): a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension. Lancet Neurol. 2018;17:405–415.
  • Mikita J, Dubourdieu-Cassagno N, Deloire MS, et al. Altered M1/M2 activation patterns of monocytes in severe relapsing experimental rat model of multiple sclerosis. Amelioration of clinical status by M2 activated monocyte administration. Mult Scler J. 2011;17:2–15.
  • Zhang X, Lund H, Parsa R, et al. Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice. Glia. 2014;62:804–817.
  • Tierney J, Kharkrang M, La Flamme A. Type-II activated macrophages supress the development of experimental autoimmune encephalomyelitis. Immunol Cell Biol. 2008;87:235–240.
  • Liao J, Seto M, Noma K. Rho kinase (ROCK) inhibitors. J Cardiovasc Pharmacol. 2007;50:17–24.
  • Guilluy C, Garcia-Mata R, Burridge K. Rho protein crosstalk: another social network? Trends Cell Biol. 2011;21:718–726.
  • Liu C, Li Y, Yu J, et al. Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. PLoS One. 2013;9:8.
  • Li YH, Xie C, Zhang Y, et al. FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms. Sci Rep. 2017;7:1–17.
  • Yan Y, Yu J, Gao Y, et al. Therapeutic potentials of the Rho kinase inhibitor Fasudil in experimental autoimmune encephalomyelitis and the related mechanisms. Metab Brain Dis. 2018;34:377-384.
  • Wu M, Nissen JC, Chen EI, et al. Tuftsin promotes an anti-inflammatory switch and attenuates symptoms in experimental autoimmune encephalomyelitis. PLoS One. 2012;7.
  • Thompson KK, Nissen JC, Pretory A, et al. Tuftsin combines with remyelinating therapy and improves outcomes in models of CNS demyelinating disease. Front Immunol. 2018;9:1–16.
  • Ponath G, Park C, Pitt D. The role of astrocytes in multiple sclerosis. Front Immunol. 2018;9:1–12.
  • Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119:7–35.
  • Kofuji P, Newman EA. Potassium buffering in the central nervous system. Neuroscience. 2004;129:1045–1056.
  • Thrane AS, Rappold PM, Fujita T, et al. Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci. 2011;108:846–851.
  • Nagelus EA, Otterson OP. Physiological roles of aquaporin-4 in brain. Phisiol Rev. 2013;93:1543–1562.
  • Papadopoulos MC, Saadoun S, Verkman AS. Aquaporins and cell migration. Eur J Physiol. 2008;456:693–700.
  • Pekny M, Pekna M. Reactive gliosis in the pathogenesis of CNS diseases. Biochim Biophys Acta - Mol Basis Dis. 2016;1862:483–491.
  • Yuan YM, He C. The glial scar in spinal cord injury and repair. Neurosci Bull. 2013;29:421–435.
  • Zhao Y, Rempe D. Targeting astrocytes for stroke therapy. Nuerotherapeutics. 2010;7:439–451.
  • Haindl MT, Köck U, Zeitelhofer-Adzemovic M, et al. The formation of a glial scar does not prohibit remyelination in an animal model of multiple sclerosis. Glia. 2019;67:467-481.
  • Kiray H, Lindsay SL, Hosseinzadeh S, et al. The multifaceted role of astrocytes in regulating myelination. Exp Neurol. 2016;283:541–549.
  • Bogler O, Wren D, Barnett SC, et al. Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. Proc Natl Acad Sci U S A. 1990;87:6368–6372.
  • Pringle N, Collarini E, Mosely M, et al. PDGF A chain homodimers drive proliferation of bipotential (0–2A) glial progenitor cells in the developing rat optic nerve. Embo J. 1989;8:1049–1056.
  • Choi JW, Gardell SE, Herr DR, et al. FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci. 2011;108:751–756.
  • Lublin F, Miller DH, Freedman MS, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387:1075–1084.
  • Bryan AM, Del Poeta M. Sphingosine-1-phosphate receptors and innate immunity. Cell Microbiol. 2018;20:1–10.
  • Li C, Chi X, Xie W, et al. Sphingosine 1-phosphate receptor 2 antagonist JTE-013 increases the excitability of sensory neurons independently of the receptor. J Neurophyisol. 2011;108:1473–1483.
  • Vollmer TL, Sorensen PS, Selmaj K, et al. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J Neurol. 2014;261:773–783.
  • Giovanni G, Barkhof F, Hartung H-P, et al. APPREGIO: a placebo-controlled trial of oral laquinimod in primary progressive multiple sclerosis.Neurology. 2018;90.
  • Thöne J, Linker RA. Laquinimod in the treatment of multiple sclerosis: A review of the data so far. Drug Des Devel Ther. 2016;10:1111–1118.
  • Strassburger-Krogias K, Ellrichmann G, Krogias C, et al. Fumarate treatment in progressive forms of multiple sclerosis: first results of a single-center observational study. Ther Adv Neurol Disord. 2014;7:232–238.
  • Galloway DA, Williams JB, Moore CS. Effects of fumarates on inflammatory human astrocyte responses and oligodendrocyte differentiation. Ann Clin Transl Neurol. 2017;4:381–391.
  • Kornberg M, Bhargava P, Kim P, et al. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science. 2018;360:449–453.
  • Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the neuromyelitis optica study group (NEMOS). J Neurol. 2014;261:1–16.
  • Tradtrantip L, Zhang H, Saadoun S, et al. Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol. 2012;71:314–322.
  • Nave K-A, Werner HB. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503–533.
  • Boggs JM. Myelin basic protein: a multifunctional protein. Cell Mol Life Sci. 2006;63:1945–1961.
  • Nadon N, West M. Myelin proteolipid protein: function in myelin structure is distinct from its role in oligodendrocyte development. Dev Neurosci. 1998;20:533–539.
  • Baumann N, Pham-Dinh D. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev. 2001;81:871–927.
  • Michalski J-P KR. Oligodendrocytes in a nutshell. Front Cell Neurosci. 2015;9:1–11.
  • Kessaris N, Fogarty M, Iannarelli P, et al. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci. 2006;9:173–179.
  • Ge W-P, Miyawaki A, Gage F, et al. Local generation of glia is a major astrocyte source in postnatal cortex. Nature. 2012;484:376–380.
  • Genoud S, Lappe-Siefke C, Goebbels S, et al. Notch1 control of oligodendrocyte differentiation in the spinal cord. J Cell Biol. 2002;158:709–718.
  • Zhang Y, Argaw AT, Gurfein BT, et al. Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination. Proc Natl Acad Sci. 2009;106:19162–19167.
  • Emery B. Regulation of oligodendrocyte differentiation and myelination. Science. 2010;330:779–782.
  • Lee Y, Morrison BM, Li Y, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487:443–448.
  • Saab AS, Tzvetanova ID, Nave KA. The role of myelin and oligodendrocytes in axonal energy metabolism. Curr Opin Neurobiol. 2013;23:1065–1072.
  • Halestrap AP, Wilson MC. The monocarboxylate transporter family-role and regulation. IUBMB Life. 2012;64:109–119.
  • Crawford AH, Tripathi RB, Foerster S, et al. Pre-existing mature oligodendrocytes do not contribute to remyelination following toxin-induced spinal cord demyelination. Am J Pathol. 2016;186:511–516.
  • Rodriguez M. Multiple sclerosis: basic concepts and hypothesis. Mayo Clin Proc. 1989;64:570–576.
  • Scolding N, Franklin R, Stevens S, et al. Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain. 1998;121:2221–2228.
  • Díez-Revuelta N, Higuero AM, Velasco S, et al. Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains. Sci Rep. 2017;7:1–13.
  • Stancic M, Slijepcevic D, Nomden A, et al. Galectin-4, a novel neuronal regulator of myelination MIRJANA. Glia. 2012;60:919–935.
  • Charlotte GHM, de Jong M, Stancic M, et al. Galectin-4, a negative regulator of oligodendrocyte differentiation, is persistently present in axons and microglia/macrophages. Synthesis (Stuttg). 2018;77:0527–0536.
  • Chen MS, Huber AB, Van Der Haar MED, et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature. 2000;403:434–439.
  • Satoh JI, Onoue H, Arima K, et al. Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. J Neuropathol Exp Neurol. 2005;64:129–138.
  • Kim M, Kang J, Theotokis P, et al. Can we design a nogo receptor-dependent cellular therapy to target MS? Cells. 2018;8:1.
  • Watzlawik JO, Warrington AE, Rodriguez M. PDGF is required for remyelination-promoting IgM stimulation of oligodendrocyte progenitor cell proliferation. PLoS One. 2013;8:1–16.
  • Nastasijevic B, Wright BR, Smestad J, et al. Remyelination induced by a DNA aptamer in a mouse model of multiple sclerosis. PLoS One. 2012;7:1–8.
  • Perschbacher K, Smestad JA, Peters JP, et al. Quantitative PCR analysis of DNA aptamer pharmacokinetics in mice. Nucleic Acid Ther. 2015;25:11–19.
  • Wilbanks B, Smestad J, Heider RM, et al. Optimization of a 40-mer anti-myelin aptamer identifies a 20-mer with enhanced properties for potential multiple sclerosis therapy. Nucleic Acid Ther. 2019; in press.
  • Tran JQ, Rana J, Barkhof F, et al. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033. Neurol Neuroimmunol Neuroinflammation. 2014;1:e18.
  • McCroskery P, Selmaj K, Fernandez O, et al. Safety and tolerability of opicinumab in relapsing multiple sclerosis: the phase 2b SYNERGY trial (P5.369). Neurology. 2017;88.
  • Cadavid D, Balcer L, Galetta S, et al. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16:189–199.
  • Ruggieri S, Tortorella C, Anti Lingo GC. 1 (Opicinumab) a new monoclonal antibody tested in relapsing remitting multiple sclerosis. Expert Rev Neurother. 2017;91:399–404.
  • Fan H, Zhao JG, Yan JQ, et al. Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination. J Cell Biochem. 2018;119:9284–9294.
  • Mei F, Fancy SPJ, Shen YAA, et al. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014;20:954–960.
  • Green AJ, Gelfand JM, Cree BA, et al. Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial. Lancet. 2017;390:2481–2489.
  • Kawabata S, Takano M, Numasawa-Kuroiwa Y, et al. Grafted human iPS cell-derived oligodendrocyte precursor cells contribute to robust remyelination of demyelinated axons after spinal cord injury. Stem Cell Reports. 2016;6:1–8.
  • Salewski RP, Mitchell RA, Li L, et al. Transplantation of induced pluripotent stem cell-derived neural stem cells mediate functional recovery following thoracic spinal cord injury through remyelination of axons. Stem Cells Transl Med. 2015;4:743–754.
  • Jaramillo-Merchán J, Jones J, Ivorra JL, et al. Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model. Cell Death Dis. 2013;4:e779.
  • Dolati S, Babaloo Z, Jadidi-Niaragh F, et al. Multiple sclerosis: therapeutic applications of advancing drug delivery systems. Biomed Pharmacother. 2017;86:343–353.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.