Tom 20, Nr 2 (2024)
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Opublikowany online: 2024-08-14
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Eksport do Mediów Społecznościowych

Eksport do Mediów Społecznościowych

„Tlące się stwardnienie rozsiane” — wyzwanie kliniczne i terapeutyczne

Natalia Niedziela, Alicja Kalinowska, Alina Kułakowska, Dagmara Mirowska-Guzel, Konrad Rejdak, Małgorzata Siger, Mariusz Stasiołek, Monika Adamczyk-Sowa
DOI: 10.5603/ppn.100783
Pol. Przegl. Neurol 2024;20(2):89-102.

Streszczenie

Wstęp. Ocena przebiegu klinicznego, zmian neuroobrazowych oraz histopatologicznych sugeruje, że stwardnienie rozsiane (SM) nie powinno być definiowane jedynie jako ogniskowa choroba zapalna ośrodkowego układu ner wowego (OUN), ponieważ istota schorzenia wynika z rozlanego, „tlącego się” procesu patofizjologicznego.
Aktualny wiedzy. Klinicznym wykładnikiem „tlącego się SM” jest postęp choroby niezależny od aktywności rzutowej (PIRA); zaś ciągła aktywacja mikrogleju jest źródłem tlącego się zapalenia i niepowodzenia remielinizacji w przebiegu choroby.
Implikacje kliniczne. Wraz z czasem trwania SM skuteczność stosowanego obecnie leczenia immunomodulującego jest mniejsza, a jego działanie niewystarczające do opanowania „tlącego się SM”. Wskazano nowe markery neuroobrazowe obejmujące paramagnetic rim lesions (PRLs) oraz wolno powiększające się zmiany (SELs), potencjalne metody oceny klinicznej oraz obiecujące opcje terapeutyczne, tj. stosowanie inhibitorów kinazy tyrozynowej Brutona (BTK inhibitors), zapobiegających PIRA w przebiegu „tlącego się SM”.
Kierunki działań w przyszłości. Innowacyjne spojrzenie na patofizjologię i pr zebieg kliniczny uzasadnia konieczność podejścia holistycznego do SM. Działania klinicystów powinny dążyć do wskazania subtelnych deficytów neurologicznych, zarówno w zakresie sprawności fizycznej jak i funkcjonowania poznawczego celem scharakteryzowania postępu choroby już we wczesnych etapach jej rozwoju. Niewątpliwie nadchodzi nowa era SM, w której wykorzystywane będą nowatorskie markery rezonansowe oraz kliniczne metody oceny „tlącego się SM”, a leczenie obejmie terapię skojarzoną, z uwzględnieniem zarówno leków zmniejszających aktywność rzutową jak i terapię hamującą progresję choroby.

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Referencje

  1. Murúa SR, Farez M, Quintana F. The immune response in multiple sclerosis. Annual Review of Pathology: Mechanisms of Disease. 2022; 17(1): 121–139.
  2. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. JAMA. 2021; 325(8): 765–779.
  3. Giovannoni G, Popescu V, Wuerfel J, et al. Smouldering multiple sclerosis: the 'real MS'. Ther Adv Neurol Disord. 2022; 15: 17562864211066751.
  4. Elliott C, Belachew S, Wolinsky JS, et al. Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis. Brain. 2019; 142(9): 2787–2799.
  5. Rissanen E, Tuisku J, Vahlberg T, et al. Microglial activation, white matter tract damage, and disability in MS. Neurol Neuroimmunol Neuroinflamm. 2018; 5(3): e443.
  6. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020; 77(9): 1132–1140.
  7. Cree BAC, Arnold DL, Chataway J, et al. Secondary progressive multiple sclerosis: new insights. Neurology. 2021; 97(8): 378–388.
  8. Slezáková D, Kadlic P, Jezberová M, et al. Brain volume loss in multiple sclerosis is independent of disease activity and might be prevented by early disease-modifying therapy. Neurol Neurochir Pol. 2023; 57(3): 282–288.
  9. Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015; 78(5): 710–721.
  10. Attfield KE, Jensen LT, Kaufmann M, et al. The immunology of multiple sclerosis. Nat Rev Immunol. 2022; 22(12): 734–750.
  11. Gresle MM, Jordan MA, Stankovich J, et al. Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells. Life Sci Alliance. 2020; 3(7).
  12. Liu R, Du S, Zhao L, et al. Autoreactive lymphocytes in multiple sclerosis: pathogenesis and treatment target. Front Immunol. 2022; 13: 996469.
  13. Stys PK, Zamponi GW, van Minnen J, et al. Will the real multiple sclerosis please stand up? Nat Rev Neurosci. 2012; 13(7): 507–514.
  14. Klistorner A, Barnett M. Remyelination trials: are we expecting the unexpected? Neurol Neuroimmunol Neuroinflamm. 2021; 8(6).
  15. Simkins TJ, Duncan GJ, Bourdette D. Chronic demyelination and axonal degeneration in multiple sclerosis: pathogenesis and therapeutic implications. Curr Neurol Neurosci Rep. 2021; 21(6): 26.
  16. Neumann B, Segel M, Chalut KJ, et al. Remyelination and ageing: reversing the ravages of time. Mult Scler. 2019; 25(14): 1835–1841.
  17. Hametner S, Dal Bianco A, Trattnig S, et al. Iron related changes in MS lesions and their validity to characterize MS lesion types and dynamics with Ultra-high field magnetic resonance imaging. Brain Pathol. 2018; 28(5): 743–749.
  18. Hametner S, Wimmer I, Haider L, et al. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. 2013; 74(6): 848–861.
  19. Stoiloudis P, Kesidou E, Bakirtzis C, et al. The role of diet and interventions on multiple sclerosis: a review. Nutrients. 2022; 14(6).
  20. Choi IY, Lee P, Adany P, et al. In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis. Mult Scler. 2018; 24(8): 1029–1038.
  21. Trapp BD, Stys PK. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009; 8(3): 280–291.
  22. Lenz KM, Nelson LH. Microglia and beyond: innate immune cells as regulators of brain development and behavioral function. Front Immunol. 2018; 9: 698.
  23. Correale J. The role of microglial activation in disease progression. Mult Scler. 2014; 20(10): 1288–1295.
  24. Ginhoux F, Greter M, Leboeuf M, et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science. 2010; 330(6005): 841–845.
  25. Ajami B, Bennett JL, Krieger C, et al. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci. 2007; 10(12): 1538–1543.
  26. Soulas C, Donahue RE, Dunbar CE, et al. Genetically modified CD34+ hematopoietic stem cells contribute to turnover of brain perivascular macrophages in long-term repopulated primates. Am J Pathol. 2009; 174(5): 1808–1817.
  27. Geissmann F, Gordon S, Hume DA, et al. Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol. 2010; 10(6): 453–460.
  28. Dong Y, Yong VW. When encephalitogenic T cells collaborate with microglia in multiple sclerosis. Nat Rev Neurol. 2019; 15(12): 704–717.
  29. Benarroch EE. Microglia: multiple roles in surveillance, circuit shaping, and response to injury. Neurology. 2013; 81(12): 1079–1088.
  30. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8(12): 958–969.
  31. Czeh M, Gressens P, Kaindl AM. The yin and yang of microglia. Dev Neurosci. 2011; 33(3-4): 199–209.
  32. Sierra A, Paolicelli RC, Kettenmann H. Cien años de microglía: milestones in a century of microglial research. Trends Neurosci. 2019; 42(11): 778–792.
  33. Luo C, Jian C, Liao Y, et al. The role of microglia in multiple sclerosis. Neuropsychiatr Dis Treat. 2017; 13: 1661–1667.
  34. Cardozo PL, de Lima IBQ, Maciel EMA, et al. Synaptic elimination in neurological disorders. Curr Neuropharmacol. 2019; 17(11): 1071–1095.
  35. Guerrero BL, Sicotte NL. Microglia in multiple sclerosis: friend or foe? Front Immunol. 2020; 11: 374.
  36. Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016; 126(7): 2597–2609.
  37. Heß K, Starost L, Kieran NW, et al. Lesion stage-dependent causes for impaired remyelination in MS. Acta Neuropathol. 2020; 140(3): 359–375.
  38. Pinto C, Cambron M, Dobai A, et al. Smoldering lesions in MS: if you like it then you should put a rim on it. Neuroradiology. 2022; 64(4): 703–714.
  39. Correale J, Gaitán MI, Ysrraelit MC, et al. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017; 140(3): 527–546.
  40. Martire MS, Moiola L, Rocca MA, et al. What is the potential of paramagnetic rim lesions as diagnostic indicators in multiple sclerosis? Expert Rev Neurother. 2022; 22(10): 829–837.
  41. Absinta M, Sati P, Masuzzo F, et al. Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 2019; 76(12): 1474–1483.
  42. Suthiphosuwan S, Sati P, Absinta M, et al. Paramagnetic rim sign in radiologically isolated syndrome. JAMA Neurol. 2020; 77(5): 653–655.
  43. Oh J, Suthiphosuwan S, Sati P, et al. Cognitive impairment, the central vein sign, and paramagnetic rim lesions in RIS. Mult Scler. 2021; 27(14): 2199–2208.
  44. Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022; 28(14): 2202–2211.
  45. Clarke MA, Pareto D, Pessini-Ferreira L, et al. Value of 3T susceptibility-weighted imaging in the diagnosis of multiple sclerosis. AJNR Am J Neuroradiol. 2020; 41(6): 1001–1008.
  46. Frischer JM, Bramow S, Dal-Bianco A, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009; 132(Pt 5): 1175–1189.
  47. Filippi M, Rocca MA, Barkhof F, et al. Attendees of the Correlation between Pathological MRI findings in MS workshop. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 2012; 11(4): 349–360.
  48. Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI. Brain. 2021; 144(3): 833–847.
  49. Elliott C, Wolinsky JS, Hauser SL, et al. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions. Mult Scler. 2019; 25(14): 1915–1925.
  50. Calvi A, Carrasco FP, Tur C, et al. MS SMART Investigators. Association of slowly expanding lesions on MRI with disability in people with secondary progressive multiple sclerosis. Neurology. 2022; 98(17): e1783–e1793.
  51. Cairns J, Vavasour IM, Traboulsee A, et al. Diffusely abnormal white matter in multiple sclerosis. J Neuroimaging. 2022; 32(1): 5–16.
  52. Abel S, Vavasour I, Lee LE, et al. Myelin damage in normal appearing white matter contributes to impaired cognitive processing speed in multiple sclerosis. J Neuroimaging. 2020; 30(2): 205–211.
  53. Giannetti P, Politis M, Su P, et al. Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome. Brain. 2015; 138(Pt 1): 110–119.
  54. Datta G, Colasanti A, Rabiner EA, et al. Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis. Brain. 2017; 140(11): 2927–2938.
  55. Bodini B, Poirion E, Tonietto M, et al. Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of worsening disability in multiple sclerosis. J Nucl Med. 2020; 61(7): 1043–1049.
  56. Sucksdorff M, Matilainen M, Tuisku J, et al. Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis. Brain. 2020; 143(11): 3318–3330.
  57. Skirková M, Mikula P, Maretta M, et al. Associations of optical coherence tomography with disability and brain MRI volumetry in patients with multiple sclerosis. Neurol Neurochir Pol. 2022; 56(4): 326–332.
  58. Chalkias IN, Bakirtzis C, Pirounides D, et al. Optical coherence tomography and optical coherence tomography with angiography in multiple sclerosis. Healthcare (Basel). 2022; 10(8).
  59. Lambe J, Saidha S, Bermel RA. Optical coherence tomography and multiple sclerosis: update on clinical application and role in clinical trials. Mult Scler. 2020; 26(6): 624–639.
  60. Green AJ, McQuaid S, Hauser SL, et al. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010; 133(Pt 6): 1591–1601.
  61. Talman LS, Bisker ER, Sackel DJ, et al. Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol. 2010; 67(6): 749–760.
  62. Ratchford JN, Saidha S, Sotirchos ES, et al. Active MS is associated with accelerated retinal ganglion cell/inner plexiform layer thinning. Neurology. 2013; 80(1): 47–54.
  63. Saidha S, Syc SB, Durbin MK, et al. Visual dysfunction in multiple sclerosis correlates better with optical coherence tomography derived estimates of macular ganglion cell layer thickness than peripapillary retinal nerve fiber layer thickness. Mult Scler. 2011; 17(12): 1449–1463.
  64. Murphy OC, Kwakyi O, Iftikhar M, et al. Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures. Mult Scler. 2020; 26(7): 815–828.
  65. Feucht N, Maier M, Lepennetier G, et al. Optical coherence tomography angiography indicates associations of the retinal vascular network and disease activity in multiple sclerosis. Mult Scler. 2019; 25(2): 224–234.
  66. Geladaris A, Torke S, Weber MS. Bruton's Tyrosine kinase inhibitors in multiple sclerosis: pioneering the path towards treatment of progression? CNS Drugs. 2022; 36(10): 1019–1030.
  67. García-Merino A. Bruton's Tyrosine kinase inhibitors: a new generation of promising agents for multiple sclerosis therapy. Cells. 2021; 10(10).
  68. Liang C, Tian D, Ren X, et al. The development of Bruton's Tyrosine kinase (BTK) inhibitors from 2012 to 2017: a mini-review. Eur J Med Chem. 2018; 151: 315–326.
  69. Hendriks RW. Drug discovery: new BTK inhibitor holds promise. Nat Chem Biol. 2011; 7(1): 4–5.
  70. Martin E, Aigrot MS, Grenningloh R, et al. Bruton's Tyrosine kinase inhibition promotes myelin repair. Brain Plast. 2020; 5(2): 123–133.
  71. Rotstein DL. All Bruton's Tyrosine kinase inhibitors have similar efficacy and risks: no. Mult Scler. 2022; 28(10): 1500–1502.
  72. Estupiñán HY, Berglöf A, Zain R, et al. Comparative analysis of BTK inhibitors and mechanisms underlying adverse effects. Front Cell Dev Biol. 2021; 9: 630942.
  73. Montalban X, Arnold DL, Weber MS, et al. Evobrutinib Phase 2 Study Group. Placebo-Controlled trial of an oral BTK inhibitor in multiple sclerosis. N Engl J Med. 2019; 380(25): 2406–2417.
  74. Reich DS, Arnold DL, Vermersch P, et al. Tolebrutinib Phase 2b Study Group. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis: a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2021; 20(9): 729–738.
  75. Gruber R, Blazier A, Lee L, et al. Evaluating the effect of BTK inhibitor tolebrutinib in human tri-culture (p1-1.virtual). Neurology. 2022; 98(18_supplement).
  76. ACTRIMS Forum 2022 - Poster Presentations. Multiple Sclerosis Journal. 2022; 28(1_suppl): 20–214.
  77. Beynon V, George IC, Elliott C, et al. Chronic lesion activity and disability progression in secondary progressive multiple sclerosis. BMJ Neurol Open. 2022; 4(1): e000240.
  78. Preziosa P, Pagani E, Moiola L, et al. Occurrence and microstructural features of slowly expanding lesions on fingolimod or natalizumab treatment in multiple sclerosis. Mult Scler. 2021; 27(10): 1520–1532.
  79. Eisele P, Wittayer M, Weber CE, et al. Impact of disease-modifying therapies on evolving tissue damage in iron rim multiple sclerosis lesions. Mult Scler. 2022; 28(14): 2294–2298.
  80. van Munster CEP, Uitdehaag BMJ. Outcome measures in clinical trials for multiple sclerosis. CNS Drugs. 2017; 31(3): 217–236.
  81. Cohen JA, Reingold SC, Polman CH, et al. International Advisory Committee on Clinical Trials in Multiple Sclerosis. Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects. Lancet Neurol. 2012; 11(5): 467–476.
  82. Cadavid D, Cohen JA, Freedman MS, et al. The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis. Mult Scler. 2017; 23(1): 94–105.
  83. Chang Ih, Kappos L, Giovannoni G, et al. Overall disability response score: an integrated endpoint to assess disability improvement and worsening over time in patients with multiple sclerosis. Mult Scler. 2022; 28(14): 2263–2273.
  84. Cadavid D, Mellion M, Hupperts R, et al. SYNERGY study investigators. 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.
  85. Lavorgna L, Brigo F, Moccia M, et al. e-Health and multiple sclerosis: an update. Mult Scler. 2018; 24(13): 1657–1664.
  86. Bradshaw MJ, Farrow S, Motl RW, et al. Wearable biosensors to monitor disability in multiple sclerosis. Neurol Clin Pract. 2017; 7(4): 354–362.
  87. Busis N. Mobile phones to improve the practice of neurology. Neurol Clin. 2010; 28(2): 395–410.
  88. Labiano-Fontcuberta A, Mato-Abad V, Álvarez-Linera J, et al. Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI. Medicine (Baltimore). 2016; 95(27): e4101.
  89. Engl C, Tiemann L, Grahl S, et al. Cognitive impairment in early MS: contribution of white matter lesions, deep grey matter atrophy, and cortical atrophy. J Neurol. 2020; 267(8): 2307–2318.
  90. Radetz A, Koirala N, Krämer J, et al. Gray matter integrity predicts white matter network reorganization in multiple sclerosis. Hum Brain Mapp. 2020; 41(4): 917–927.
  91. Tahedl M, Levine SM, Greenlee MW, et al. Functional connectivity in multiple sclerosis: recent findings and future directions. Front Neurol. 2018; 9: 828.
  92. Chard D, Trip SA. Resolving the clinico-radiological paradox in multiple sclerosis. F1000Res. 2017; 6: 1828.
  93. Cree BAC, Hollenbach JA, Bove R, et al. University of California, San Francisco MS-EPIC Team. Silent progression in disease activity-free relapsing multiple sclerosis. Ann Neurol. 2019; 85(5): 653–666.
  94. Deczkowska A, Amit I, Schwartz M. Microglial immune checkpoint mechanisms. Nat Neurosci. 2018; 21(6): 779–786.
  95. Benedict RHB, Amato MP, DeLuca J, et al. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol. 2020; 19(10): 860–871.
  96. Owens TD, Smith PF, Redfern A, et al. Phase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib (PRN2246, SAR442168). Clin Transl Sci. 2022; 15(2): 442–450.
  97. Herman AE, Chinn LW, Kotwal SG, et al. Safety, pharmacokinetics, and pharmacodynamics in healthy volunteers treated with GDC-0853, a selective reversible Bruton's Tyrosine kinase inhibitor. Clin Pharmacol Ther. 2018; 103(6): 1020–1028.
  98. Becker A, Martin EC, Mitchell DY, et al. Safety, tolerability, pharmacokinetics, target occupancy, and concentration-qt analysis of the novel BTK inhibitor evobrutinib in healthy volunteers. Clin Transl Sci. 2020; 13(2): 325–336.
  99. Zhang D, Gong He, Meng F. Recent advances in BTK inhibitors for the treatment of inflammatory and autoimmune diseases. Molecules. 2021; 26(16).
  100. Kaul M, End P, Cabanski M, et al. Remibrutinib (LOU064): a selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase i trial. Clin Transl Sci. 2021; 14(5): 1756–1768.