Modern mechanisms and strategies of pharmacotherapy of remyelination in multiple sclerosis | Український Медичний Часопис

Multiple sclerosis is an immune-mediated neurodegenerative disease of the central nervous system characterized by demyelination, loss of oligodendroglia and axonal pathology. Although significant progress has been made in developing immunomodulatory treatments to reduce myelin damage and slow the progression of multiple sclerosis, treatment options for many pathophysiological aspects of the disease are lacking. Currently available immune-centered treatments can reduce the immune-mediated damage found in multiple sclerosis patients, but they cannot eliminate possible remyelination failure or irreversible neuronal damage that occurs during multiple sclerosis progression. Recent advances have provided a better understanding of remyelination processes, including the progression of oligodendrocyte cells after demyelination. In addition, new results have been obtained that highlight the various components of the microenvironment that contribute to myelin repair and axon repair. The difficulties of myelin recovery after immune-mediated central nervous system damage, the contribution of experimental models of multiple sclerosis in providing an understanding of myelin recovery, as well as current and potential therapeutic targets associated with remyelination are considered.

Refences

1. Нефьодов О.О., Кальбус О.І. (2022) Механізми виникнення та хронізації нейропатичного болю при розсіяному склерозі в клінічних та експериментальних умовах. Укр. мед. часопис, 1–2(147–148): 7–11.
2. Trapp B.D., Nave K.A. (2008) Multiple sclerosis: An immune or neurodegenerative disorder? Annu Rev. Neurosci., 31: 247–269.
3. Baird J.F., Cederberg K.L.J., Sikes E.M. et al. (2019) Physical activity and walking performance across the lifespan among adults with multiple sclerosis. Mult. Scler. Relat. Disord., 35: 36–41.
4. Benedict R.H.B., Amato M.P., DeLuca J. et al. (2020) Cognitive impairment in multiple sclerosis: Clinical management, MRI, and therapeutic avenues. Lancet Neurol., 19(10): 860–871.
5. Lubetzki C., Zalc B., Williams A. et al. (2020) Remyelination in multiple sclerosis: From basic science to clinical translation. Lancet Neurol., 19(8): 678–688.
6. Plemel J.R., Liu W.Q., Yong V.W. (2017) Remyelination therapies: A new direction and challenge in multiple sclerosis. Nat. Rev. Drug Discov., 16(9): 617–634.
7. Melchor G.S., Khan T., Reger J.F., Huang J.K. (2019) Remyelination Pharmacotherapy Investigations Highlight Diverse Mechanisms Underlying Multiple Sclerosis Progression. ACS Pharmacol. Transl. Sci., 2(6): 372–386. doi: 10.1021/acsptsci.9b00068
8. Kremer D., Gottle P., Flores-Rivera J. et al. (2019;) Remyelination in multiple sclerosis: From concept to clinical trials. Curr. Opin. Neurol., 32(3): 378–384.
9. Cui Q.L., Kuhlmann T., Miron V.E. et al. (2013) Oligodendrocyte progenitor cell susceptibility to injury in multiple sclerosis. Am. J. Pathol., 183(2): 516–525.
10. Pu A., Stephenson E.L., Yong V.W. (2018) The extracellular matrix: Focus on oligodendrocyte biology and targeting CSPGs for remyelination therapies. Glia, 66(9): 1809–1825.
11. Thompson A.J. (2018) Commentary on the ECTRIMS-EAN guideline for pharmacological treatment of multiple sclerosis. Ther. Adv. Neurol. Disord., 11: 1–2.
12. Ineichen B.V., Plattner P.S., Good N. et al. (2017) Nogo-A antibodies for progressive multiple sclerosis. CNS Drugs, 31(3): 187–198.
13. Kremer D., Gottle P., Hartung H.P. et al. (2016) Pushing Forward: Remyelination as the New Frontier in CNS Diseases. Trends Neurosci., 39(4): 246–263.
14. Allanach J.R., Farrell J.W., Mésidor M. et al. (2021) Current status of neuroprotective and neuroregenerative strategies in multiple sclerosis: A systematic review (https://journals.sagepub.com/doi/full/10.1177/13524585211008760).
15. Smith K., McDonald W., Blakemore W. (1979) Restoration of secure conduction by central demyelination. Trans. Am. Neurol. Assoc., 104: 25–29.
16. Smith K.J., McDonald W.I. (1999) The pathophysiology of multiple sclerosis the mechanisms underlying the production of symptoms and the natural history of the disease. Philos Trans R. Soc. Lond. B. Biol. Sci., 354(1390): 1649–1673.
17. Duncan I.D., Brower A., Kondo Y. et al. (2009) Extensive remyelination of the CNS leads to functional recovery. Proc. Natl. Acad. Sci. USA, 106(16): 6832–6836.
18. Fünfschilling U., Supplie L.M., Mahad D. et al. (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature, 485(7399): 517–521.
19. Morrison B.M., Lee Y., Rothstein J.D. (2013) Oligodendroglia: metabolic supporters of axons. Trends Cell Biol., 23(12): 644–651.
20. Irvine K.A., Blakemore W.F. (2008) Remyelination protects axons from demyelination-associated axon degeneration. Brain, 131(6): 1464–1477.
21. Mei F., Lehmann-Horn K., Shen Y.-A.A. et al. (2016) Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. eLife. ;5:e18246.
22. Sampaio-Baptista C., Johansen-Berg H. (2017) White matter plasticity in the adult brain. Neuron, 96(6): 1239–1251.
23. Franklin R.J.M., French-Constant C. (2017) Regenerating CNS myelin — from mechanisms to experimental medicines. Nat. Rev. Neurosci., 18: 753.
24. Franklin R.J.M., French-Constant C., Edgar J.M., Smith K.J. (2012) Neuroprotection and repair in multiple sclerosis. Nat. Rev. Neurol., 8: 624.
25. Patani R., Balaratnam M., Vora A., Reynolds R. (2007) Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathol. Appl. Neurobiol., 33(3): 277–287.
26. Patrikios P., Stadelmann C., Kutzelnigg A. et al. (2006) Remyelination is extensive in a subset of multiple sclerosis patients. Brain, 129(12): 3165–3172.
27. Bodini B., Veronese M., García-Lorenzo D. et al. (2016) Dynamic imaging of individual remyelination profiles in multiple sclerosis. Ann. Neurol., 79(5): 726–738.
28. Bramow S., Frischer J.M., Lassmann H. et al. (2010) Demyelination versus remyelination in progressive multiple sclerosis. Brain, 133(10): 2983–2998.
29. Jeffries M.A., Urbanek K., Torres L. et al. (2016) ERK1/2 Activation in preexisting oligodendrocytes of adult mice drives new myelin synthesis and enhanced CNS function. J. Neurosci., 36(35): 9186–9200.
30. Crawford A.H., Tripathi R.B., Foerster S. et al. (2016) Pre-Existing mature oligodendrocytes do not contribute to remyelination following toxin-induced spinal cord demyelination. Am. J. Pathol., 186(3): 511–516.
31. French-Constant C., Raff M.C. (1986) Proliferating bipotential glial progenitor cells in adult rat optic nerve. Nature, 319: 499.
32. Zawadzka M., Rivers L.E., Fancy S.P.J. et al. (2010) CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem. Cell, 6(6): 578–590.
33. Psachoulia K., Jamen F., Young K.M., Richardson W.D. (2009) Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol., 5(3–4): 57–67.
34. Blakemore W.F. (1974) Pattern of remyelination in the CNS. Nature, 249(5457): 577–578.
35. Wolswijk G. (1998) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci., 18(2): 601.
36. Hughes E.G., Kang S.H., Fukaya M., Bergles D.E. (2013) Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain. Nat. Neurosci., 16(6): 668–676.
37. Franklin R.J.M., Gilson J.M., Blakemore W.F. (1997) Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system. J. Neurosci. Res., 50(2): 337–344.
38. Hammond T.R., Gadea A., Dupree J. et al. (2014) Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron, 81(3): 588–602.
39. Liddelow S.A., Guttenplan K.A., Clarke L.E. et al. (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 18(541): 481.
40. Wake H., Lee P.R., Fields R.D. (2011) Control of local protein synthesis and initial events in myelination by action potentials. Science, 333(6049): 1647.
41. Birchmeier C., Nave K. (2008) Neuregulin-1, a key axonal signal that drives Schwann cell growth and differentiation. Glia, 56(14): 1491–1497.
42. Almeida R., Lyons D. (2016) Oligodendrocyte development in the absence of their target axons in vivo. PLoS ONE, 11(10): e0164432.
43. Mei F., Fancy S.P.J., Shen Y.-A.A. et al. (2014) Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat. Med., 20(8): 954–960.
44. Klingseisen A., Lyons D.A. (2017) Axonal regulation of central nervous system myelination: structure and function. Neuroscientist., 24(1): 7–21.
45. Rawji K.S., Yong V.W. (2013) The benefits and detriments of macrophages/microglia in models of multiple sclerosis. Clin. Dev. Immunol., 2013: 948976.
46. Döring A., Sloka S., Lau L. et al. (2015) Stimulation of monocytes, macrophages, and microglia by amphotericin B and macrophage colony-stimulating factor promotes remyelination. J. Neurosci., 35(3): 1136.
47. Yong V.W., Rivest S. (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron, 64(1): 55–60.
48. Miron V.E., Boyd A., Zhao J.-W. et al. (2013) M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat. Neurosci., 16(9): 1211–1218.
49. Frischer J.M., Weigand S.D., Guo Y. et al. (2015) Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann. Neurol., 78(5): 710–721.
50. Goldschmidt T., Antel J., König F.B. et al. (2009) Remyelination capacity of the MS brain decreases with disease chronicity. Neurology, 72(22): 1914.
51. Oh J., Lee Y.D., Wagers A.J. (2014) Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat. Med., 20(8): 870–880.
52. van Wijngaarden P., Franklin R.J.M. (2013) Ageing stem and progenitor cells: implications for rejuvenation of the central nervous system. Development, 140(12): 2562.
53. Neumann B., Baror R., van Wijngaarden P., Franklin R.J. (2017) Remyelination of regenerating axons. Acta Ophthalmola, 95(S259). 10.1111/j.1755-3768.2017.03525.
54. Kitada M., Rowitch D.H. (2006) Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord. Glia, 54(1): 35–46.
55. Kuhlmann T., Miron V., Cuo Q. et al. (2008) Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain, 131(7): 1749–1758.
56. Chang A., Staugaitis S.M., Dutta R. et al. (2012) Cortical remyelination: a new target for repair therapies in multiple sclerosis. Ann. Neurol., 72(6): 918–926.