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Review

New targets and therapeutics for neuroprotection, remyelination and repair in multiple sclerosis

ORCID Icon & ORCID Icon
Pages 443-459 | Received 29 Jan 2020, Accepted 15 Apr 2020, Published online: 29 Apr 2020

References

  • Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378(2):169–180. Epub 2018/01/11. PubMed PMID: 29320652.
  • Faer S, Plemel JR, Gold R, et al. Progressive multiple sclerosis: from pathophysiology to therapeutic strategies. Nat Rev Drug Discov. 2019;18(12):905–922. Epub 2019/ 08/11. PubMed PMID: 31399729.
  • Faer S, Gold R. Efficacy and safety of the newer multiple sclerosis drugs approved since 2010. CNS Drugs. 2018;32(3):269–287. Epub 2018/03/31. PubMed PMID: 29600441.
  • De Angelis F, Plantone D, Chataway J. Pharmacotherapy in secondary progressive multiple sclerosis: an overview. CNS Drugs. 2018;32(6):499–526. Epub 2018/ 07/04. PubMed PMID: 29968175.
  • Narayan RN, Forsthuber T, Stuve O. Emerging drugs for primary progressive multiple sclerosis. Expert Opin Emerg Drugs. 2018;23(2):97–110. Epub 2018/04/12. PubMed PMID: 29638150.
  • Bennett CF. Therapeutic antisense oligonucleotides are coming of age. Annu Rev Med. 2019;70:307–321. Epub 2019/01/30. PubMed PMID: 30691367.
  • Wagner FB, Mignardot JB, Le Goff-Mignardot CG, et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018;563(7729):65–71. Epub 2018/11/02. PubMed PMID: 30382197.
  • Halpern CH, Santini V, Lipsman N, et al. Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology. 2019;93(24):e2284–e93. Epub 2019/11/22. PubMed PMID: 31748250.
  • Villoslada P. Neuroprotective therapies for multiple sclerosis and other demyelinating diseases. Mult Scl Dem Dis. 2016;1(1):1–11.
  • Plemel JR, Liu WQ, Yong VW. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nat Rev Drug Discov. 2017;16(9):617–634. PubMed PMID: 28685761.
  • Kotelnikova E, Kiani NA, Abad E, et al. Dynamics and heterogeneity of brain damage in multiple sclerosis. PLoS Comput Biol. 2017;13(10):e1005757. PubMed PMID: 29073203.
  • Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–286.
  • Chung KK, Altmann D, Barkhof F, et al. A thirty year clinical and MRI observational study of multiple sclerosis and clinically isolated syndromes. Ann Neurol. 2019;87(1):63–74. Epub 2019/ 11/07. PubMed PMID: 31693200.
  • Kantarci OH, Zeydan B, Atkinson EJ, et al. Relapse recovery: the forgotten variable in multiple sclerosis clinical trials. Neurol Neuroimmunol Neuroinflamm. 2020;7(2). Epub 2019/ 12/19. PubMed PMID: 31848231.
  • Signori A, Gallo F, Bovis F, et al. Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: a systematic review and meta-analysis. Mult Scler Relat Disord. 2016;6:57–63. Epub 2016/ 04/12. PubMed PMID: 27063624.
  • Carassiti D, Altmann DR, Petrova N, et al. Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex. Neuropathol Appl Neurobiol. 2018;44(4):377–390. Epub 2017/ 04/19. PubMed PMID: 28419506.
  • Vesterinen HM, Connick P, Irvine CM, et al. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis. PLoS One. 2015;10(4):e0117705. Epub 2015/ 04/10. PubMed PMID: 25856304;
  • Franklin RJ, ffrench-Constant C, Edgar JM, et al. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol. 2012;8(11):624–634. Epub 2012/10/03. PubMed PMID: 23026979. .
  • Lipton SA. Pathologically activated therapeutics for neuroprotection. Nat Rev Neurosci. 2007;8(10):803–808. Epub 2007/ 09/21. doi: nrn2229 [pii] 10.1038/nrn2229. PubMed PMID: 17882256.
  • Luo H, Broux B, Wang X, et al. EphrinB1 and EphrinB2 regulate T cell chemotaxis and migration in experimental autoimmune encephalomyelitis and multiple sclerosis. Neurobiol Dis. 2016;91:292–306. Epub 2016/04/04. PubMed PMID: 27039370. .
  • Nicoletti F, Mazzon E, Fagone P, et al. Prevention of clinical and histological signs of MOG-induced experimental allergic encephalomyelitis by prolonged treatment with recombinant human EGF. J Neuroimmunol. 2019;332:224–232. Epub 2019/05/18. PubMed PMID: 31100693. .
  • Diem R, Molnar F, Beisse F, et al. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol. BMJ Open. 2016;6(3):e010956. PubMed PMID: 26932144;.
  • Ruffini F, Furlan R, Poliani PL, et al. Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Ther. 2001;8(16):1207–1213. Epub 2001/08/18. PubMed PMID: 11509953.
  • Gao X, Deng L, Wang Y, et al. GDNF enhances therapeutic efficiency of neural stem cells-based therapy in chronic experimental allergic encephalomyelitis in rat. Stem Cells Int. 2016;2016:1431349. Epub 2016/05/24. PubMed PMID: 27212951.
  • Frank JA, Richert N, Lewis B, et al. A pilot study of recombinant insulin-like growth factor-1 in seven multiple sderosis patients. Mult Scler. 2002;8(1):24–29. Epub 2002/04/09. PubMed PMID: 11936485.
  • Allender E, Deol H, Schram S, et al. Neuregulin1 modulation of experimental autoimmune encephalomyelitis (EAE). J Neuroimmunol. 2018;318:56–64. Epub 2018/03/15. PubMed PMID: 29534847. .
  • Kopec BM, Kiptoo P, Zhao L, et al. Non-invasive brain delivery and efficacy of BDNF to stimulate neuroregeneration and suppression of disease relapse in EAE mice. Mol Pharm. 2019. Epub 2019/12/18. PubMed PMID: 31846344.
  • Fang M, He D, Zhang F, et al. Antineuroinflammatory and neurotrophic effects of CNTF and C16 peptide in an acute experimental autoimmune encephalomyelitis rat model. Front Neuroanat. 2013;7:44. Epub 2014/ 01/15. PubMed PMID: 24416000.
  • Gresle MM, Alexandrou E, Wu Q, et al. Leukemia inhibitory factor protects axons in experimental autoimmune encephalomyelitis via an oligodendrocyte-independent mechanism. PLoS One. 2012;7(10):e47379. Epub 2012/10/19. PubMed PMID: 23077604.
  • Di Marco R, Khademi M, Wallstrom E, et al. Curative effects of recombinant human Interleukin-6 in DA rats with protracted relapsing experimental allergic encephalomyelitis. J Neuroimmunol. 2001;116(2):168–177. Epub 2001/07/05. PubMed PMID: 11438171.
  • Mango D, Nistico R, Furlan R, et al. PDGF modulates synaptic excitability and short-latency afferent inhibition in multiple sclerosis. Neurochem Res. 2019;44(3):726–733. Epub 2018/ 02/03. PubMed PMID: 29392518.
  • Bjarnadottir K, Benkhoucha M, Merkler D, et al. B cell-derived transforming growth factor-beta1 expression limits the induction phase of autoimmune neuroinflammation. Sci Rep. 2016;6:34594. Epub 2016/10/07. PubMed PMID: 27708418.
  • McKenzie BA, Mamik MK, Saito LB, et al. Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis. Proc Natl Acad Sci U S A. 2018;115(26):E6065–E74. Epub 2018/06/14. PubMed PMID: 29895691.
  • Miller R, Bradley W, Cudkowicz M, et al. Phase II/III randomized trial of TCH346 in patients with ALS. Neurology. 2007;69(8):776–784. Epub 2007/08/22. PubMed PMID: 17709710.
  • Olanow CW, Schapira AH, LeWitt PA, et al. TCH346 as a neuroprotective drug in Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2006;5(12):1013–1020. Epub 2006/ 11/18. PubMed PMID: 17110281.
  • Wang Y, Guo L, Wang J, et al. Necrostatin-1 ameliorates the pathogenesis of experimental autoimmune encephalomyelitis by suppressing apoptosis and necroptosis of oligodendrocyte precursor cells. Exp Ther Med. 2019;18(5):4113–4119. Epub 2019/10/16. PubMed PMID: 31611942.
  • Zhang S, Su Y, Ying Z, et al. RIP1 kinase inhibitor halts the progression of an immune-induced demyelination disease at the stage of monocyte elevation. Proc Natl Acad Sci U S A. 2019;116(12):5675–5680. Epub 2019/03/07. PubMed PMID: 30837313
  • De Sarno P, Axtell RC, Raman C, et al. Lithium prevents and ameliorates experimental autoimmune encephalomyelitis. J Immunol. 2008;181(1):338–345. Epub 2008/06/21. PubMed PMID: 18566399.
  • Dolati S, Aghebati-Maleki L, Ahmadi M, et al. Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double-blind, placebo-controlled trial. J Cell Physiol. 2018;233(7):5222–5230. Epub 2017/ 12/02. PubMed PMID: 29194612.
  • Lv J, Du C, Wei W, et al. The antiepileptic drug valproic acid restores T cell homeostasis and ameliorates pathogenesis of experimental autoimmune encephalomyelitis. J Biol Chem. 2012;287(34):28656–28665. Epub 2012/06/27. PubMed PMID: 22733814.
  • Unal G, Dokumaci AH, Ozkartal CS, et al. Famotidine has a neuroprotective effect on MK-801 induced toxicity via the Akt/GSK-3beta/beta-catenin signaling pathway in the SH-SY5Y cell line. Chem Biol Interact. 2019;314:108823. Epub 2019/09/30. PubMed PMID: 31563592.
  • Green LK, Zareie P, Templeton N, et al. Enhanced disease reduction using clozapine, an atypical antipsychotic agent, and glatiramer acetate combination therapy in experimental autoimmune encephalomyelitis. Mult Scler J Exp Transl Clin. 2017;3(1):2055217317698724. Epub 2017/ 06/14. PubMed PMID: 28607752.
  • Giacoppo S, Soundara Rajan T, De Nicola GR, et al. Moringin activates Wnt canonical pathway by inhibiting GSK3beta in a mouse model of experimental autoimmune encephalomyelitis. Drug Des Devel Ther. 2016;10:3291–3304. Epub 2016/10/28. PubMed PMID: 27784989.
  • Deslauriers AM, Afkhami-Goli A, Paul AM, et al. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J Immunol. 2011;187(9):4788–4799. Epub 2011/10/04. PubMed PMID: 21964030.
  • De Giglio L, Marinelli F, Barletta VT, et al. Effect on cognition of estroprogestins combined with interferon beta in multiple sclerosis: analysis of secondary outcomes from a randomised controlled trial. CNS Drugs. 2017;31(2):161–168. Epub 2016/ 12/21. PubMed PMID: 27995531.
  • Vukusic S, Ionescu I, El-Etr M, et al. The Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART’MUS) trial: rationale, objectives and state of advancement. J Neurol Sci. 2009;286(1–2):114–118. Epub 2009/ 09/18. PubMed PMID: 19758607.
  • Pantzaris MC, Loukaides GN, Ntzani EE, et al. A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial. BMJ Open. 2013;3(4):e002170. Epub 2013/ 04/20. PubMed PMID: 23599375.
  • Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122–2133. Epub 2017/06/01. PubMed PMID: 28564557.
  • Yang C, Yu L, Kong L, et al. Pyrroloquinoline quinone (PQQ) inhibits lipopolysaccharide induced inflammation in part via downregulated NF-kappaB and p38/JNK activation in microglial and attenuates microglia activation in lipopolysaccharide treatment mice. PLoS One. 2014;9(10):e109502. Epub 2014/ 10/15. PubMed PMID: 25314304.
  • Gandy KAO, Zhang J, Nagarkatti P, et al. Resveratrol (3, 5, 4ʹ-Trihydroxy-trans-Stilbene) attenuates a mouse model of multiple sclerosis by altering the miR-124/sphingosine kinase 1 axis in encephalitogenic T cells in the brain. J Neuroimmune Pharmacol. 2019;14(3):462–477. Epub 2019/ 04/04. PubMed PMID: 30941623.
  • Ghaiad HR, Nooh MM, El-Sawalhi MM, et al. Resveratrol promotes remyelination in cuprizone model of multiple sclerosis: biochemical and histological study. Mol Neurobiol. 2017;54(5):3219–3229. Epub 2016/ 04/14. PubMed PMID: 27067589.
  • Torres KJ, Gottle P, Kremer D, et al. Vinpocetine inhibits oligodendroglial precursor cell differentiation. Cell Physiol Biochem. 2012;30(3):711–722. Epub 2012/ 08/03. PubMed PMID: 22854710.
  • Riva N, Mora G, Soraru G, et al. Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019;18(2):155–164. Epub 2018/ 12/18. PubMed PMID: 30554828.
  • Blanchard B, Heurtaux T, Garcia C, et al. Tocopherol derivative TFA-12 promotes myelin repair in experimental models of multiple sclerosis. J Neurosci. 2013;33(28):11633–11642. Epub 2013/07/12. PubMed PMID: 23843531.
  • Lovera J, Ramos A, Devier D, et al. Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: phase I single group and phase II randomized placebo-controlled studies. J Neurol Sci. 2015;358(1–2):46–52. Epub 2015/ 08/25. PubMed PMID: 26298797.
  • Mahler A, Steiniger J, Bock M, et al. Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial. Am J Clin Nutr. 2015;101(3):487–495. Epub 2015/ 03/04. PubMed PMID: 25733633.
  • Yadav V, Marracci GH, Munar MY, et al. Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters. Mult Scler. 2010;16(4):387–397. Epub 2010/ 02/13. PubMed PMID: 20150394.
  • Sanoobar M, Eghtesadi S, Azimi A, et al. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci. 2015;18(4):169–176. Epub 2014/ 03/14. PubMed PMID: 24621064.
  • Moccia M, Capacchione A, Lanzillo R, et al. Coenzyme Q10 supplementation reduces peripheral oxidative stress and inflammation in interferon-beta1a-treated multiple sclerosis. Ther Adv Neurol Disord. 2019;12:1756286418819074. Epub 2019/03/01. PubMed PMID: 30815035 .
  • Villoslada P, Rovira A, Montalban X, et al. Effects of diazoxide in multiple sclerosis: a randomized, double-blind phase 2 clinical trial. Neurol Neuroimmunol Neuroinflamm. 2015;2(5):e147. Epub 2015/ 09/26. PubMed PMID: 26405686.
  • Lee MJ, Jang M, Choi J, et al. Korean red ginseng and ginsenoside-Rb1/-Rg1 alleviate experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells and upregulating regulatory T cells. Mol Neurobiol. 2016;53(3):1977–2002. Epub 2015/04/08. PubMed PMID: 25846819.
  • Sorensen PS, Lycke J, Eralinna JP, et al. Simvastatin as add-on therapy to interferon beta-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691–701. Epub 2011/ 07/12. PubMed PMID: 21742556.
  • Lovera JF, Frohman E, Brown TR, et al. Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Mult Scler. 2010;16(6):715–723. Epub 2010/05/21. PubMed PMID: 20483885.
  • Peyro Saint Paul L, Creveuil C, Heinzlef O, et al. Efficacy and safety profile of memantine in patients with cognitive impairment in multiple sclerosis: a randomized, placebo-controlled study. J Neurol Sci. 2016;363:69–76. Epub 2016/ 03/24. PubMed PMID: 27000224. .
  • Kalkers NF, Barkhof F, Bergers E, et al. The effect of the neuroprotective agent riluzole on MRI parameters in primary progressive multiple sclerosis: a pilot study. Mult Scler. 2002;8(6):532–533. Epub 2002/12/12. PubMed PMID: 12474997.
  • Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–1107. Epub 2012/09/21. PubMed PMID: 22992073.
  • Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–1097. Epub 2012/09/21. PubMed PMID: 22992072.
  • Naismith RT, Wolinsky JS, Wundes A, et al. Diroximel fumarate (DRF) in patients with relapsing-remitting multiple sclerosis: interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study. Mult Scler. 2019;1352458519881761. Epub 2019/ 11/05. PMID: 31680631
  • Sakurai K, Zou JP, Tschetter JR, et al. Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2002;129(1–2):186–196. Epub 2002/08/06. PubMed PMID: 12161035.
  • Tullius SG, Biefer HR, Li S, et al. NAD+ protects against EAE by regulating CD4+ T-cell differentiation. Nat Commun. 2014;5:5101. Epub 2014/ 10/08. PubMed PMID: 25290058 .
  • van Noort JM, Bsibsi M, Nacken PJ, et al. Therapeutic intervention in multiple sclerosis with Alpha B-crystallin: a randomized controlled Phase IIa trial. PLoS One. 2015;10(11):e0143366. Epub 2015/ 11/26. PubMed PMID: 26599332
  • Zabala A, Vazquez-Villoldo N, Rissiek B, et al. P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. EMBO Mol Med. 2018;10(8). Epub 2018/07/06. PubMed PMID: 29973381
  • Cambron M, Mostert J, D’Hooghe M, et al. Fluoxetine in progressive multiple sclerosis: the FLUOX-PMS trial. Mult Scler. 2019;25(13):1728–1735. Epub 2019/ 06/21. PubMed PMID: 31218911.
  • Schwartzbach CJ, Grove RA, Brown R, et al. Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study. J Neurol. 2017;264(2):304–315. Epub 2016/ 11/27. PubMed PMID: 27888416.
  • Fox RJ, Coffey CS, Conwit R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med. 2018;379(9):846–855. Epub 2018/ 08/30. PubMed PMID: 30157388.
  • Vermersch P, Benrabah R, Schmidt N, et al. Masitinib treatment in patients with progressive multiple sclerosis: a randomized pilot study. BMC Neurol. 2012 12;12(1):36. Epub 2012/ 06/14. PubMed PMID: 22691628.
  • Raftopoulos R, Hickman SJ, Toosy A, et al. Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(3):259–269. PubMed PMID: 26822749.
  • Solaro C, Restivo D, Mancardi GL, et al. Oxcarbazepine for treating paroxysmal painful symptoms in multiple sclerosis: a pilot study. Neurol Sci. 2007;28(3):156–158. Epub 2007/ 07/03. PubMed PMID: 17603770.
  • Kapoor R, Furby J, Hayton T, et al. Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Neurol. 2010;9(7):681–688. Epub 2010/ 07/14. PubMed PMID: 20621711.
  • McKee JB, Cottriall CL, Elston J, et al. Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial. Mult Scler. 2019;25(2):246–255. Epub 2017/ 11/28. PubMed PMID: 29172994.
  • Goodman AD, Bethoux F, Brown TR, et al. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: results of open-label extensions of two Phase 3 clinical trials. Mult Scler. 2015;21(10):1322–1331. Epub 2015/ 01/15. PubMed PMID: 25583832.
  • Villoslada P, Hauser SL, Bartke I, et al. Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med. 2000;191(10):1799–1806. PubMed PMID: 10811872.
  • Colafrancesco V, Villoslada P. Targeting NGF pathway for developing neuroprotective therapies for multiple sclerosis and other neurological diseases. Arch Ital Biol. 2011;149(2):183–192. Epub 2011/06/28. PubMed PMID: 21701990.
  • Cudkowicz ME, Katz J, Moore DH, et al. Toward more efficient clinical trials for amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11(3):259–265. PubMed PMID: 19961263.
  • Apfel SC. Nerve growth factor for the treatment of diabetic neuropathy: what went wrong, what went right, and what does the future hold? Int Rev Neurobiol. 2002;50:393–413. PubMed PMID: 12198818.
  • Kazim SF, Iqbal K. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease. Mol Neurodegener. 2016;11(1):50. Epub 2016/07/13. PubMed PMID: 27400746.
  • Ding C, Hammarlund M. Mechanisms of injury-induced axon degeneration. Curr Opin Neurobiol. 2019;(57):171–178. Epub 2019/05/10. PubMed PMID: 31071521.
  • Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci. 2014;15(6):394–409. PubMed PMID: 24840802.
  • Adalbert R, Coleman MP. Review: axon pathology in age-related neurodegenerative disorders. Neuropathol Appl Neurobiol. 2013;39(2):90–108. PubMed PMID: 23046254.
  • Krauss R, Bosanac T, Engber T, et al., editors. Small molecule inhibitors of SARM1 prevent axonal degeneration in vitro and in vivo. In: Neurosciences 2019. Meeting of the Society for Neuroscience; 2019.
  • Le Pichon CE, Meilandt WJ, Dominguez S, et al. Loss of dual leucine zipper kinase signaling is protective in animal models of neurodegenerative disease. Sci Transl Med. 2017;9(403):eaag0394. Epub 2017/08/18. PubMed PMID: 28814543.
  • Grievink HW, Heuberger J, Huang F, et al. DNL104, a centrally penetrant RIPK1 inhibitor, inhibits RIP1 kinase phosphorylation in a randomized Phase I ascending dose study in healthy volunteers. Clin Pharmacol Ther. 2019. Epub 2019/ 08/23. PubMed PMID: 31437302.
  • Parkinson Study G. The safety and tolerability of a mixed lineage kinase inhibitor (CEP-1347) in PD. Neurology. 2004;62(2):330–332. Epub 2004/ 01/28. PubMed PMID: 14745084.
  • Villoslada P, Vila G, Colafrancesco V, et al. Axonal and myelin neuroprotection by the peptoid BN201 in brain inflammation. Neurotherapeutics. 2019;16(3):808–827. Epub 2019/ 03/01. PubMed PMID: 30815844 .
  • 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(Pt 3):678–692. Epub 2011/03/01. PubMed PMID: 21354971.
  • Peruzzotti-Jametti L, Pluchino S. Targeting mitochondrial metabolism in neuroinflammation: towards a therapy for progressive multiple sclerosis. Trends Mol Med. 2018;24(10);838–855. Epub 2018/ 08/14. PubMed PMID: 30100517.
  • Heidker RM, Emerson MR, LeVine SM. Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis. Neural Regen Res. 2017;12(8):1262–1267. Epub 2017/10/03. PubMed PMID: 28966637.
  • Sedel F, Bernard D, Mock DM, et al. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2016;110(Pt B):644–653. Epub 2016/10/30. PubMed PMID: 26327679.
  • Tourbah A, Lebrun-Frenay C, Edan G, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: a randomised, double-blind, placebo-controlled study. Mult Scler. 2016;22(13):1719–1731. Epub 2016/ 09/03. PubMed PMID: 27589059.
  • Cree BA, Cutter G, Wolinsky JS, et al. Results of the Phase 3 SPI2 study of MD1003 (high dose Pharmaceutical grade Biotin) in progressive MS. Neurology American Academy of Neurology meeting Toronoto 2020. 2020; Abstract #S40.002
  • Platten M, Nollen EAA, Rohrig UF, et al. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019;18(5):379–401. Epub 2019/02/15. PubMed PMID: 30760888.
  • Platten M, Ho PP, Youssef S, et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science. 2005;310(5749):850–855. Epub 2005/ 11/08. PubMed PMID: 16272121.
  • Moreno B, Hevia H, Santamaria M, et al. Methylthioadenosine reverses brain autoimmune disease. Ann Neurol. 2006;60:323–334. PMID: 1678653
  • Moreno B, Lopez I, Fernandez-Diez B, et al. Differential neuroprotective effects of 5ʹ-deoxy-5ʹ-methylthioadenosine. PLoS One. 2014;9(3):e90671. Epub 2014/03/07. PubMed PMID: 24599318.
  • Waxman SG. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nat Rev Neurosci. 2006;7(12):932–941. PubMed PMID: 17115075.
  • Waxman SG. Mechanisms of disease: sodium channels and neuroprotection in multiple sclerosis-current status. Nat Clin Pract Neurol. 2008;4(3):159–169. PubMed PMID: 18227822.
  • Connick P, De Angelis F, Parker RA, et al. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis. BMJ Open. 2018;8(8):e021944. Epub 2018/ 09/01. PubMed PMID: 30166303;.
  • Chataway J, De Angelis F, Connick P, et al. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020;19(3):214–225. Epub 2020/ 01/26. PubMed PMID: 31981516.
  • Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006 Feb;5(2):160-70.PMID: 16424917.
  • Villoslada P, Arrondo G, Sepulcre J, et al. Memantine induces reversible neurologic impairment in patients with MS. Neurology. 2008;72(19):1630–1633. Epub 2008/12/19. PubMed PMID: 19092106.
  • Green AJ. Understanding pseudo: the symptoms are real, the cause is unclear. Neurology. 2009;72(19):1626–1627. PubMed PMID: 19246422.
  • Giunti D, Parodi B, Cordano C, et al. Can we switch microglia’s phenotype to foster neuroprotection? Focus on multiple sclerosis. Immunology. 2014;141(3):328–339. PubMed PMID: 24116890.
  • Rottlaender A, Kuerten S. Stepchild or prodigy? Neuroprotection in Multiple Sclerosis (MS) research. Int J Mol Sci. 2015;16(7):14850–14865. PubMed PMID: 26140377.
  • Hernangomez M, Mestre L, Correa FG, et al. CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation. Glia. 2012;60(9):1437–1450. PubMed PMID: 22653796.
  • Vecino E, Rodriguez FD, Ruzafa N, et al. Glia-neuron interactions in the mammalian retina. Prog Retin Eye Res. 2015;51:1–40. PubMed PMID: 26113209.
  • Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19(8):987–991. Epub 2016/07/28. PubMed PMID: 27459405.
  • Stangel M, Kuhlmann T, Matthews PM, et al. Achievements and obstacles of remyelinating therapies in multiple sclerosis. Nat Rev Neurol. 2017;13(12):742–754. Epub 2017/11/18. PubMed PMID: 29146953.
  • Cole KLH, Early JJ, Lyons DA. Drug discovery for remyelination and treatment of MS. Glia. 2017;65(10):1565–1589. Epub 2017/06/16. PubMed PMID: 28618073.
  • Bove RM, Green AJ. Remyelinating pharmacotherapies in multiple sclerosis. Neurotherapeutics. 2017;14(4):894–904. Epub 2017/09/28. PubMed PMID: 289485339.
  • Baldassari LE, Feng J, Clayton BLL, et al. Developing therapeutic strategies to promote myelin repair in multiple sclerosis. Expert Rev Neurother. 2019;19(10):997–1013. Epub 2019/06/20. PubMed PMID: 31215271. .
  • Kolahdouzan M, Futhey NC, Kieran NW, et al. Novel molecular leads for the prevention of damage and the promotion of repair in neuroimmunological disease. Front Immunol. 2019;10:1657. Epub 2019/08/06. PubMed PMID: 31379852.
  • Nave KA. Myelination and support of axonal integrity by glia. Nature. 2010;468(7321):244–252. Epub 2010/ 11/12. . PubMed PMID: 21068833.
  • Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535–561. Epub 2008/06/19. PubMed PMID: 18558866.
  • Kutzelnigg A, Lassmann H. Pathology of multiple sclerosis and related inflammatory demyelinating diseases. Handb Clin Neurol. 2014;122:15–58. PubMed PMID: 24507512.
  • DeLuca GC, Williams K, Evangelou N, et al. The contribution of demyelination to axonal loss in multiple sclerosis. Brain. 2006;129(Pt 6):1507–1516. Epub 2006/ 04/07. PubMed PMID: 16597651.
  • Fancy SP, Chan JR, Baranzini SE, et al. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci. 2011;34:21–43. Epub 2011/ 06/23. PubMed PMID: 21692657.
  • 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(3):189–199. Epub 2017/ 02/24. PubMed PMID: 28229892.
  • Cadavid D, Mellion M, Hupperts R, et al. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019;18(9):845–856. Epub 2019/ 07/10. PubMed PMID: 31285147.
  • Ineichen BV, Kapitza S, Bleul C, et al. Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology. Acta Neuropathol. 2017;134(3):423–440. Epub 2017/06/25. PubMed PMID: 28646336.
  • Eisen A, Greenberg BM, Bowen JD, et al. A double-blind, placebo-controlled, single ascending-dose study of remyelinating antibody rHIgM22 in people with multiple sclerosis. Mult Scler J Exp Transl Clin. 2017;3(4):2055217317743097. Epub 2018/ 01/20. PubMed PMID: 29348926.
  • Deshmukh VA, Tardif V, Lyssiotis CA, et al. A regenerative approach to the treatment of multiple sclerosis. Nature. 2013;502(7471):327–332. Epub 2013/ 10/11. PubMed PMID: 24107995.
  • Mei F, Fancy SP, Shen YA, et al. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014;20(8):954–960. PubMed PMID: 24997607.
  • Najm FJ, Madhavan M, Zaremba A, et al. Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature. 2015;522(7555):216–220. Epub 2015/04/22. PubMed PMID: 25896324.
  • Hubler Z, Allimuthu D, Bederman I, et al. Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination. Nature. 2018;560(7718):372–376. Epub 2018/ 07/27. PubMed PMID: 30046109.
  • 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(10111):2481–2489. Epub 2017/ 10/17. PubMed PMID: 29029896.
  • Chan D, Binks S, Nicholas JM, et al. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol. 2017;16(8):591–600. Epub 2017/ 06/11. PubMed PMID: 28600189.
  • Chataway J, Schuerer N, Alsanousi A, et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014;383(9936):2213–2221. Epub 2014/ 03/25. PubMed PMID: 24655729.
  • Derfuss T, Curtin F, Guebelin C, et al. A phase IIa randomised clinical study of GNbAC1, a humanised monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus in multiple sclerosis patients. Mult Scler. 2015;21(7):885–893. Epub 2014/ 11/14. PubMed PMID: 25392325.
  • Mei F, Guo S, He Y, et al. Quetiapine, an atypical antipsychotic, is protective against autoimmune-mediated demyelination by inhibiting effector T cell proliferation. PLoS One. 2012;7(8):e42746. Epub 2012/08/23. PubMed PMID: 22912731.
  • Chedrawe MAJ, Holman SP, Lamport AC, et al. Pioglitazone is superior to quetiapine, clozapine and tamoxifen at alleviating experimental autoimmune encephalomyelitis in mice. J Neuroimmunol. 2018;321:72–82. Epub 2018/06/30. PubMed PMID: 29957391.
  • Shirani A, Okuda DT, Stuve O. Therapeutic advances and future prospects in progressive forms of multiple sclerosis. Neurotherapeutics. 2016;13(1):58–69. Epub 2016/01/06. PubMed PMID: 26729332.
  • Way SW, Podojil JR, Clayton BL, et al. Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic. Nat Commun. 2015;6:6532. Epub 2015/03/15. PubMed PMID: 25766071 .
  • Ingwersen J, De Santi L, Wingerath B, et al. Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis. J Neurochem. 2018;146(1):86–98. Epub 2018/02/24. PubMed PMID: 29473171.
  • Silva RBM, Greggio S, Venturin GT, et al. Beneficial effects of the calcium channel blocker CTK 01512-2 in a mouse model of multiple sclerosis. Mol Neurobiol. 2018;55(12):9307–9327. Epub 2018/04/19. PubMed PMID: 29667130.
  • Yuan XL, Zhao YP, Huang J, et al. A Kv1.3 channel-specific blocker alleviates neurological impairment through inhibiting T-cell activation in experimental autoimmune encephalomyelitis. CNS Neurosci Ther. 2018;24(10):967–977. Epub 2018/03/27. PubMed PMID: 29577640.
  • Schampel A, Volovitch O, Koeniger T, et al. Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis. Proc Natl Acad Sci U S A. 2017;114(16):E3295–E304. Epub 2017/04/07. PubMed PMID: 28381594.
  • Mowry EM, Pelletier D, Gao Z, et al. Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection. Eur J Neurol. 2016;23(2):327–332. Epub 2015/11/01. PubMed PMID: 26518224.
  • Chandraratna RA, Noelle RJ, Nowak EC. Treatment with retinoid X receptor agonist IRX4204 ameliorates experimental autoimmune encephalomyelitis. Am J Transl Res. 2016;8(2):1016–1026. Epub 2016/05/10.PubMed PMID: 27158387.
  • Wang J, Sui RX, Miao Q, et al. Effect of Fasudil on remyelination following cuprizone-induced demyelination. CNS Neurosci Ther. 2019. Epub 2019/ 05/28. PubMed PMID: 31124292.
  • Li YH, Xie C, Zhang Y, et al. FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms. Sci Rep. 2017;7:41227. Epub 2017/01/24. PubMed PMID: 28112256 .
  • Zeldich E, Chen CD, Avila R, et al. The anti-aging protein klotho enhances remyelination following cuprizone-induced demyelination. J Mol Neurosci. 2015;57(2):185–196. Epub 2015/06/13. PubMed PMID: 26067431.
  • Yu X, Cheng G, Zhang L, et al. N-Phenylquinazolin-2-amine Yhhu4952 as a novel promotor for oligodendrocyte differentiation and myelination. Sci Rep. 2018;8(1):14040. Epub 2018/09/21. PubMed PMID: 30232349.
  • Fancy SP, Harrington EP, Yuen TJ, et al. Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination. Nat Neurosci. 2011;14(8):1009–1016. Epub 2011/06/28. PubMed PMID: 21706018.
  • Ou Z, Sun Y, Lin L, et al. Olig2-targeted G-protein-coupled receptor Gpr17 regulates oligodendrocyte survival in response to lysolecithin-induced demyelination. J Neurosci. 2016;36(41):10560–10573. Epub 2016/10/14. PubMed PMID: 27733608.
  • Namchaiw P, Wen H, Mayrhofer F, et al. Temporal and partial inhibition of GLI1 in neural stem cells (NSCs) results in the early maturation of NSC derived oligodendrocytes in vitro. Stem Cell Res Ther. 2019;10(1):272. Epub 2019/08/29. PubMed PMID: 31455382.
  • Kuroda M, Muramatsu R, Maedera N, et al. Peripherally derived FGF21 promotes remyelination in the central nervous system. J Clin Invest. 2017;127(9):3496–3509. Epub 2017/08/22. PubMed PMID: 28825598.
  • Nguyen HTH, Wood RJ, Prawdiuk AR, et al. TrkB agonist LM22A-4 increases oligodendroglial populations during myelin repair in the corpus callosum. Front Mol Neurosci. 2019;12:205. Epub 2019/09/12. PubMed PMID: 31507374. .
  • Du C, Duan Y, Wei W, et al. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination. Nat Commun. 2016;7:11120. Epub 2016/ 04/05. PubMed PMID: 27040771 .
  • Zhang J, Zhang ZG, Lu M, et al. MiR-146a promotes oligodendrocyte progenitor cell differentiation and enhances remyelination in a model of experimental autoimmune encephalomyelitis. Neurobiol Dis. 2019;125:154–162. Epub 2019/02/02. PubMed PMID: 30707940.
  • D’Intino G, Lorenzini L, Fernandez M, 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):778–790. Epub 2011/06/29. PubMed PMID: 21707794.
  • Jurynczyk M, Jurewicz A, Bielecki B, et al. Overcoming failure to repair demyelination in EAE: gamma-secretase inhibition of Notch signaling. J Neurol Sci. 2008;265(1–2):5–11. Epub 2007/ 10/24. PubMed PMID: 17949754.
  • Li Y, Zhang Y, Han W, et al. TRO19622 promotes myelin repair in a rat model of demyelination. Int J Neurosci. 2013;123(11):810–822. Epub 2013/05/15. PubMed PMID: 23668883.
  • Baradaran S, Hajizadeh Moghaddam A, Ghasemi-Kasman M. Hesperetin reduces myelin damage and ameliorates glial activation in lysolecithin-induced focal demyelination model of rat optic chiasm. Life Sci. 2018;207:471–479. Epub 2018/07/31. PubMed PMID: 30056861.
  • Naeimi R, Baradaran S, Ashrafpour M, et al. Querectin improves myelin repair of optic chiasm in lyolecithin-induced focal demyelination model. Biomed Pharmacother. 2018;101:485–493. Epub 2018/03/05. PubMed PMID: 29501770.
  • Caillaud M, Chantemargue B, Richard L, et al. Local low dose curcumin treatment improves functional recovery and remyelination in a rat model of sciatic nerve crush through inhibition of oxidative stress. Neuropharmacology. 2018;139:98–116. Epub 2018/07/19. PubMed PMID: 30018000. .
  • Gaesser JM, Fyffe-Maricich SL. Intracellular signaling pathway regulation of myelination and remyelination in the CNS. Exp Neurol. 2016;283(Pt B):501–511. Epub 2016/03/10. PubMed PMID: 26957369.
  • Hammond TR, Gadea A, Dupree J, et al. Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron. 2014;81(3):588–602. Epub 2014/02/11. PubMed PMID: 24507193.
  • Swire M, Kotelevtsev Y, Webb DJ, et al. Endothelin signalling mediates experience-dependent myelination in the CNS. Elife. 2019;8. Epub 2019/10/29. PubMed PMID: 31657718
  • Watkins TA, Emery B, Mulinyawe S, et al. Distinct stages of myelination regulated by gamma-secretase and astrocytes in a rapidly myelinating CNS coculture system. Neuron. 2008;60(4):555–569. Epub 2008/11/29. PubMed PMID: 19038214
  • Smith ES, Jonason A, Reilly C, et al. SEMA4D compromises blood-brain barrier, activates microglia, and inhibits remyelination in neurodegenerative disease. Neurobiol Dis. 2015;73:254–268. Epub 2014/ 12/03. PubMed PMID: 25461192. .
  • Biname F, Pham-Van LD, Spenle C, et al. Disruption of Sema3A/Plexin-A1 inhibitory signalling in oligodendrocytes as a therapeutic strategy to promote remyelination. EMBO Mol Med. 2019;11(11):e10378. Epub 2019/10/01. PubMed PMID: 31566924.
  • Bernard F, Moreau-Fauvarque C, Heitz-Marchaland C, et al. Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination. Glia. 2012;60(10):1590–1604. Epub 2012/07/11. PubMed PMID: 22777942.
  • LaGanke C, Samkoff L, Edwards K, et al. Safety/tolerability of the anti-semaphorin 4D antibody VX15/2503 in a randomized phase 1 trial. Neurol Neuroimmunol Neuroinflamm. 2017;4(4):e367. Epub 2017/ 06/24. PubMed PMID: 28642891.
  • Spitsin SV, Scott GS, Mikheeva T, et al. Comparison of uric acid and ascorbic acid in protection against EAE. Free Radic Biol Med. 2002;33(10):1363–1371. Epub 2002/11/07. PubMed PMID: 12419468.
  • Guo YE, Suo N, Cui X, et al. Vitamin C promotes oligodendrocytes generation and remyelination. Glia. 2018;66(7):1302–1316. Epub 2018/02/10. PubMed PMID: 29423921; PubMed Central PMCID: PMCPMC6001564.
  • Andorra M, Alba-Arbalat S, Camos-Carreras A, et al. Using acute optic neuritis trials to assess neuroprotective and remyelinating therapies in multiple sclerosis. JAMA Neurol. 2019. Epub 2019/10/01. PubMed PMID: 31566686.
  • Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;376(11):1038–1046. Epub 2017/03/16. PubMed PMID: 28296613.
  • Lanza C, Morando S, Voci A, et al. Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo. J Neurochem. 2009;110(5):1674–1684. Epub 2009/ 07/22. doi: JNC6268 [pii] 10.1111/j.1471-4159.2009.06268.x. PubMed PMID: 19619133..
  • Scolding NJ, Pasquini M, Reingold SC, et al. International conference on cell-based therapies for multiple S, international conference on cell-based therapies for multiple S, et al. Cell-based therapeutic strategies for multiple sclerosis. Brain. 2017;140(11):2776–2796. Epub 2017/10/21. PubMed PMID: 29053779
  • Genc B, Bozan HR, Genc S, et al. Stem cell therapy for multiple sclerosis. Adv Exp Med Biol. 2019;1084:145–174. Epub 2018/ 07/25. PubMed PMID: 30039439.
  • Orack JC, Deleidi M, Pitt D, et al. Concise review: modeling multiple sclerosis with stem cell biological platforms: toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration. Stem Cells Transl Med. 2015;4(3):252–260. Epub 2015/ 01/17. PubMed PMID: 25593207.
  • Sharrack B, Saccardi R, Alexander T, et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2019. Epub 2019/ 09/29. PubMed PMID: 31558790.
  • Sormani MP, Muraro PA, Schiavetti I, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology. 2017;88(22):2115–2122. Epub 2017/ 04/30. PubMed PMID: 28455383.
  • Llufriu S, Sepulveda M, Blanco Y, et al. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis. PLoS One. 2014;9(12):e113936. PubMed PMID: 25436769.
  • Oliveira AG, Goncalves M, Ferreira H, et al. Growing evidence supporting the use of mesenchymal stem cell therapies in multiple sclerosis: A systematic review. Mult Scler Relat Disord. 2019;38:101860. Epub 2019/ 11/26. PubMed PMID: 31765999.
  • Uccelli A, Laroni A, Brundin L, et al. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019;20(1):263. Epub 2019/ 05/11. PubMed PMID: 31072380;.
  • Skaper SD. Oligodendrocyte precursor cells as a therapeutic target for demyelinating diseases. Prog Brain Res. 2019;245:119–144. Epub 2019/04/10. PubMed PMID: 30961866.
  • Hermanto Y, Maki T, Takagi Y, et al. Xeno-free culture for generation of forebrain oligodendrocyte precursor cells from human pluripotent stem cells. J Neurosci Res. 2019;97(7):828–845. Epub 2019/03/21. PubMed PMID: 30891830.
  • Di Ruscio A, Patti F, Welner RS, et al. Multiple sclerosis: getting personal with induced pluripotent stem cells. Cell Death Dis. 2015;6:e1806. Epub 2015/ 07/15. PubMed PMID: 26158512.
  • Thiruvalluvan A, Czepiel M, Kap YA, et al. Survival and functionality of human induced pluripotent stem cell-derived oligodendrocytes in a nonhuman primate model for multiple sclerosis. Stem Cells Transl Med. 2016;5(11):1550–1561. Epub 2016/07/13. PubMed PMID: 27400790
  • Laterza C, Merlini A, De Feo D, et al. iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. Nat Commun. 2013;4:2597. Epub 2013/10/31. PubMed PMID: 24169527. .
  • Nishri Y, Hampton D, Ben-Shushan E, et al. Continuous immune-modulatory effects of human Olig2+ precursor cells attenuating a chronic-active model of multiple sclerosis. Mol Neurobiol. 2019. Epub 2019/10/28. PubMed PMID: 31656989.
  • Ottoboni L, Merlini A, Martino G. Neural stem cell plasticity: advantages in therapy for the injured central nervous system. Front Cell Dev Biol. 2017;5:52. Epub 2017/ 05/30. PubMed PMID: 28553634.
  • Butti E, Bacigaluppi M, Chaabane L, et al. Neural stem cells of the subventricular zone contribute to neuroprotection of the corpus callosum after cuprizone-induced demyelination. J Neurosci. 2019;39(28):5481–5492. Epub 2019/05/30. PubMed PMID: 31138656
  • Butti E, Cusimano M, Bacigaluppi M, et al. Neurogenic and non-neurogenic functions of endogenous neural stem cells. Front Neurosci. 2014;8:92. Epub 2014/05/09. PubMed PMID: 24808821
  • Harris VK, Stark J, Vyshkina T, et al. Phase I trial of intrathecal mesenchymal stem cell-derived neural progenitors in progressive multiple sclerosis. EBioMedicine. 2018;29:23–30. Epub 2018/02/17. PubMed PMID: 29449193 .
  • Demicheva E, Cui YF, Bardwell P, et al. Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep. 2015;10(11):1887–1898. Epub 2015/03/25. PubMed PMID: 25801027.
  • Ziemann A, Rosebraugh M, Barger B, et al. A Phase 1, multiple-dose study of Elezanumab (ABT-555) in patients with relapsing forms of multiple sclerosis. Neurology. 2019;92:1.
  • Wahl AS, Omlor W, Rubio JC, et al. Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science. 2014;344(6189):1250–1255. Epub 2014/ 06/14. PubMed PMID: 24926013.
  • Meininger V, Genge A, van den Berg LH, et al. Safety and efficacy of ozanezumab in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16(3):208–216. Epub 2017/ 02/01. PubMed PMID: 28139349.
  • Steinman L. No quiet surrender: molecular guardians in multiple sclerosis brain. J Clin Invest. 2015;125(4):1371–1378. Epub 2015/04/02. PubMed PMID: 25831441 .
  • Ho PP, Kanter JL, Johnson AM, et al. Identification of naturally occurring fatty acids of the myelin sheath that resolve neuroinflammation. Sci Transl Med. 2012;4(137):137ra73. Epub 2012/06/08. PubMed PMID: 22674551.
  • Zhang MA, Rego D, Moshkova M, et al. Peroxisome proliferator-activated receptor (PPAR)alpha and -gamma regulate IFNgamma and IL-17A production by human T cells in a sex-specific way. Proc Natl Acad Sci U S A. 2012;109(24):9505–9510. Epub 2012/ 06/01. PubMed PMID: 22647601.
  • Lovett-Racke AE, Hussain RZ, Northrop S, et al. Peroxisome proliferator-activated receptor alpha agonists as therapy for autoimmune disease. J Immunol. 2004;172(9):5790–5798. Epub 2004/04/22. PubMed PMID: 15100326.
  • Chabas D, Baranzini SE, Mitchell D, et al. The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 2001;294(5547):1731–1735. Epub 2001/ 11/27. PubMed PMID: 11721059.
  • Lock C, Hermans G, Pedotti R, et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med. 2002;8(5):500–508. Epub 2002/05/02. PubMed PMID: 11984595.
  • Han MH, Hwang SI, Roy DB, et al. Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets. Nature. 2008;451(7182):1076–1081. Epub 2008/ 02/19. PubMed PMID: 18278032.
  • Rothbard JB, Rothbard JJ, Soares L, et al. Identification of a common immune regulatory pathway induced by small heat shock proteins, amyloid fibrils, and nicotine. Proc Natl Acad Sci USA. 2018;115(27):7081–7086. Epub 2018/06/20. PubMed PMID: 29915045
  • Rothbard JB, Kurnellas MP, Ousman SS, et al. Small heat shock proteins, amyloid fibrils, and nicotine stimulate a common immune suppressive pathway with implications for future therapies. Cold Spring Harb Perspect Med. 2019;9(7):a034223. Epub 2018/ 09/27. PubMed PMID: 30249602.
  • Dunn SE, Youssef S, Goldstein MJ, et al. Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. J Exp Med. 2006;203(2):401–412. Epub 2006/02/16. PubMed PMID: 16476765
  • Lanzillo R, Moccia M, Russo CV, et al. Therapeutic lag in reducing disability progression in relapsing-remitting multiple sclerosis: 8-year follow-up of two randomized add-on trials with atorvastatin. Mult Scler Relat Disord. 2019;28:193–196. Epub 2019/ 01/10. PubMed PMID: 30623857.
  • Zamvil SS, Steinman L. Combining statins with interferon beta in multiple sclerosis: think twice, it might not be all right. Lancet Neurol. 2011;10(8):672–673. Epub 2011/ 07/12. PubMed PMID: 21742557.
  • Subramanian S, Shahaf G, Ozeri E, et al. Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+ Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice. Metab Brain Dis. 2011;26(2):107–113. Epub 2011/03/26. PubMed PMID: 21437674.
  • Paul BD, Sbodio JI, Xu R, et al. Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature. 2014;509(7498):96–100. Epub 2014/ 03/29. PubMed PMID: 24670645.
  • Chora AA, Fontoura P, Cunha A, et al. Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation. J Clin Invest. 2007;117(2):438–447. Epub 2007/01/27. PubMed PMID: 17256058; PubMed Central PMCID: PMCPMC1770945.
  • Morikawa T, Kajimura M, Nakamura T, et al. Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway. Proc Natl Acad Sci U S A. 2012;109(4):1293–1298. Epub 2012/01/11. PubMed PMID: 22232681
  • Kotelnikova E, Bernardo-Faura M, Silberberg G, et al. Signaling networks in MS: a systems-based approach to developing new pharmacological therapies. Mult Scler. 2015;21(2):138–146. PubMed PMID: 25112814.
  • Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov. 2016;15(4):275–292. Epub 2016/ 01/23. PubMed PMID: 26794270.
  • Oller-Salvia B, Sanchez-Navarro M, Giralt E, et al. Blood-brain barrier shuttle peptides: an emerging paradigm for brain delivery. Chem Soc Rev. 2016;45(17):4690–4707. Epub 2016/05/18. PubMed PMID: 27188322.
  • Abrahao A, Meng Y, Llinas M, et al. First-in-human trial of blood-brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound. Nat Commun. 2019;10(1):4373. Epub 2019/09/29. PubMed PMID: 31558719.
  • Oh J, Ontaneda D, Azevedo C, et al. Imaging outcome measures of neuroprotection and repair in MS: a consensus statement from NAIMS. Neurology. 2019;92(11):519–533. Epub 2019/ 02/23. PubMed PMID: 30787160.
  • Matthews PM. Chronic inflammation in multiple sclerosis - seeing what was always there. Nat Rev Neurol. 2019. Epub 2019/08/20. PubMed PMID: 31420598.
  • Andorra M, Nakamura K, Lampert EJ, et al. Assessing biological and methodological aspects of brain volume loss in multiple sclerosis. JAMA Neurol. 2018;75(10):1246–1255. Epub 2018/07/05. PubMed PMID: 29971335.
  • Martinez-Lapiscina E, Sanchez-Dalmau B, Fraga-Pumar E, et al. The visual pathway as a model to understand brain damage in multiple sclerosis. Mult Scler. 2014;20(13):1678–1685. PubMed PMID: 25013155.
  • Balcer LJ, Balk LJ, Brandt AU, et al. The international multiple sclerosis visual system consortium: advancing visual system research in multiple sclerosis. J Neuroophthalmol. 2018;38(4):494–501. Epub 2018/ 11/13. PubMed PMID: 30418332.
  • Pulido-Valdeolivas I, Zubizarreta I, Martinez-Lapiscina E, et al. Precision medicine for multiple sclerosis: an update of the available biomarkers and their use in therapeutic decision making. Expert Rev Precis Med Drug Dev. 2017;2(6):1–17.
  • Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018(10);14:577–589. Epub 2018/09/02. PubMed PMID: 30171200.
  • Athauda D, Gulyani S, Karnati HK, et al. Utility of neuronal-derived exosomes to examine molecular mechanisms that affect motor function in patients with parkinson disease: a secondary analysis of the exenatide-PD trial. JAMA Neurol. 2019;76(4):420–429. Epub 2019/01/15. PubMed PMID: 30640362;

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