Article Sidebar

Submitted
Apr 12, 2024
Published
Apr 12, 2024
Download
PDF
Statistic
Read Counter : 28 Download : 21

Main Article Content

Abstract

This comprehensive review explores the intricate landscape of multiple sclerosis (MS), a complex autoimmune disease affecting millions worldwide. Beginning with an analysis of its etiology, including genetic predisposition, environmental factors, and immune dysregulation, the article delves into the pathophysiological mechanisms underlying MS, highlighting inflammation, neurodegeneration, and gliosis as central features. Clinical presentations and diagnostic considerations are discussed, emphasizing the diverse neurological symptoms and objective findings encountered in MS patients. The review further examines current management strategies, focusing on disease-modifying drugs and emerging therapies such as botanical extracts, probiotics, and novel immunomodulatory agents. Insights from preclinical studies investigating the therapeutic potential of natural compounds like Hypericum perforatum, Panax ginseng, Nigella sativa, and ginger are presented alongside discussions on bee venom and blueberries as potential adjunctive treatments. Finally, the article explores ongoing clinical trials evaluating innovative therapeutic approaches targeting immune dysregulation in MS. Through a multidimensional lens, this review offers valuable insights into the complexities of MS pathogenesis and the evolving landscape of therapeutic interventions

Keywords

Multiple sclerosis Autoimmune disease gliosis Nigella sativa Hypericum perforatum Panax ginseng

Article Details

How to Cite
Zeenath P, Mumthas Beegum PC, Mohammed Sahad P, E. Tamil Jothi, G Babu, & Anson S Maroky. (2024). Advancements in Multiple Sclerosis Research: From Pathogenesis to Novel Therapeutic Strategies. International Journal of Research in Pharmacology & Pharmacotherapeutics, 13(2), 54-62. Retrieved from https://ijrpp.com/ijrpp/article/view/531
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. 1. Abdel-Maged AES, Gad AM, Rashed LA, Azab SS, Mohamed EA, Awad AS. Repurposing of Secukinumab as Neuroprotective in Cuprizone-Induced Multiple Sclerosis Experimental Model via Inhibition of Oxidative, Inflammatory, and Neurodegenerative Signaling. Molecular Neurobiology. 2020 Jun 8;57(8):3291–306.
  2. 2. McDonnell GV, Hawkins SA (1996) Primary progressive multiple sclerosis: a distinct syndrome? Mult Scler J 2(3):137–141
  3. 3. Thompson AJ et al (1997) Primary progressive multiple sclerosis. Brain 120(6):1085–1096
  4. 4. Noyes K, Weinstock-Guttman B. Impact of diagnosis and early treatment on the course of multiple sclerosis. Am J Manag Care. 2013 Nov;19(17 Suppl):s321-31. PMID: 24494633.
  5. 5. University of California, San Francisco MS-EPIC Team:, Cree BAC, Gourraud PA, Oksenberg JR, Bevan C, Crabtree-Hartman E, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Annals of Neurology [Internet]. 2016 Oct 1;80(4):499–510.
  6. 6. Aldhahri, R.S.; Alghamdi, B.S.; Alzahrani, N.A.; Bahaidrah, K.A.; Alsufiani, H.M.; Mansouri, R.A.; Ashraf, G.M. Biochanin A Improves Memory Decline and Brain Pathology in Cuprizone-Induced Mouse Model of Multiple Sclerosis. Behav. Sci. 2022, 12, 70. https://doi.org/10.3390/bs12030070
  7. 7. Benedict RHB, Amato MP, DeLuca J, Geurts JJG. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. The Lancet Neurology. 2020 Oct;19(10):860–71.
  8. 8. Stadelmann C, Wegner C, Bruck W (2011) Inflammation, demyelination, and degeneration—recent insights from MS pathology. Biochim Biophys Acta 1812(2):275–282
  9. 9. Klineova S, Lublin FD. Clinical course of multiple sclerosis. Cold Spring Harb. Perspect. Med. 8, a028928 (2018).
  10. 10. Freedman MS, Selchen D, Arnold DL et al. Treatment optimization in MS: Canadian MS working group updated recommendations. Can. J. Neurol. Sci. 40, 307–323 (2013).
  11. 11. Mulder WJM, Ochando J, Joosten LAB, Fayad ZA, Netea MG: Therapeutic targeting of trained immunity. Nat Rev Drug Discov. 2019, 18:553-66. 10.1038/s41573-019-0025-4
  12. 12. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G: Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010, 9:727-39. 10.1016/S1474-4422(10)70094-6
  13. 13. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT: Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol. 2003, 134:128-32. 10.1016/S0165-5728(02)00396-X
  14. 14. Ntranos A, Lublin F: Diagnostic criteria, classification and treatment goals in multiple sclerosis: the chronicles of time and space. Curr Neurol Neurosci Rep. 2016, 16:90. 10.1007/s11910-016-0688-8
  15. 15. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B: Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry. 2011, 82:1132-41. 10.1136/jnnp.2011.240432
  16. 16. Sintzel MB, Rametta M, Reder AT: Vitamin D and multiple sclerosis: a comprehensive review . Neurol Ther. 2018, 7:59-85. 10.1007/s40120-017-0086-4
  17. 17. Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC: Twin concordance and sibling recurrence rates in multiple sclerosis. Proc Natl Acad Sci U S A. 2003, 100:12877-82. 10.1073/pnas.1932604100
  18. 18. Dighriri IM, Aldalbahi AA, Albeladi F, Tahiri AA, Kinani EM, Almohsen RA, Alamoudi NH, Alanazi AA, Alkhamshi SJ, Althomali NA, Alrubaiei SN. An overview of the history, pathophysiology, and pharmacological interventions of multiple sclerosis. Cureus. 2023 Jan 2;15(1).
  19. 19. Lucchinetti CF, Popescu BF, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med. 2011;365(23):2188- 2197. doi:10.1056/NEJMoa1100648
  20. 20. 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. doi:10.1093/brain/awp070
  21. 21. Michel L, Touil H, Pikor NB, Gommerman JL, Prat A, Bar-Or A. B cells in the multiple sclerosis central nervous system: trafficking and contribution to CNS-compartmentalized inflammation. Front Immunol. 2015;6:636. doi:10.3389/fimmu.2015. 00636
  22. 22. Ramagopalan SV, Dobson R, Meier UC, Giovannoni G: Multiple sclerosis: risk factors, prodromes, and potential causal pathways. Lancet Neurol. 2010, 9:727-39
  23. 23. Golan D, Halhal B, Glass-Marmor L, et al.: Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties. BMC Neurol. 2013, 13:60. 1
  24. 24. Sadovnick AD, Ebers GC: Epidemiology of multiple sclerosis: a critical overview . Can J Neurol Sci. 1993, 20:17-29. 10.1017/s0317167100047351
  25. 25. Hayes CE, Nashold FE, Spach KM, Pedersen LB: The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-grand). 2003, 49:277-300
  26. 26. Rodriguez M: Multiple sclerosis: basic concepts and hypothesis . Mayo Clin Proc. 1989, 64:570-6. 10.1016/s0025-6196(12)65563-3 34.
  27. 27. Miller DH, Leary SM: Primary-progressive multiple sclerosis . Lancet Neurol. 2007, 6:903-12. 10.1016/S1474- 4422(07)70243-0 35.
  28. 28. Robertson NP, Fraser M, Deans J, Clayton D, Walker N, Compston DA: Age-adjusted recurrence risks for relatives of patients with multiple sclerosis. Brain. 1996, 119:449-55.
  29. 29. Poser CM: The role of trauma in the pathogenesis of multiple sclerosis: a review . Clin Neurol Neurosurg. 1994, 96:103-10.
  30. 30. McGinley MP, Goldschmidt CH, Rae-Grant AD. Diagnosis and treatment of multiple sclerosis: a review. Jama. 2021 Feb 23;325(8):765-79.
  31. 31. Krajnc N, Bsteh G, Berger T, Mares J, Hartung HP: Monoclonal antibodies in the treatment of relapsing multiple sclerosis: an overview with emphasis on pregnancy, vaccination, and risk management. Neurotherapeutics. 2022, 19:753-73.
  32. 32. Beaubrun G, Gray GE. A review of herbal medicines for psychiatric disorders. Psychiatr Serv 2000;51(9):1130-4. doi: 10.1176/appi.ps.51.9.1130
  33. 33. Kiasalari Z, Baluchnejadmojarad T, Roghani M. Hypericum perfo ratum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson’s disease. Cell Mol Neurobiol 2016;36:521–30.
  34. 34. Naseri M, Ahmadi A, Gharegozli K, Nabavi M, Faghihzadeh S, Ashtarian N, Montazami F, Rezaeizadeh H. A double blind, placebo-controlled, crossover study on the effect of MS14, an herbalmarine drug, on quality of life in patients with multiple sclerosis. J Med Plant Res 2009;3:271–5.
  35. 35. Cho IH. Effects of Panax ginseng in Neurodegenerative Diseases. J Ginseng Res 2012;36:342–53.
  36. 36. Lee MJ, Jang M, Choi J, Chang BS, Kim do Y, Kim SH, Kwak YS, Oh S, Lee JH, Chang BJ, Nah SY, Cho IH. 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;53:1977–2002.
  37. 37. Etemadifar M, Sayahi F, Abtahi SH, Shemshaki H, Dorooshi GA, Goodarzi M, Akbari M, Fereidan-Esfahani M. Ginseng in the treatment of fatigue in multiple sclerosis: a randomized, placebo-controlled, double-blind pilot study. Int J Neurosci 2013;123:480–6.
  38. 38. Cho YJ, Son HJ, Kim KS. A 14-week randomized, placebocontrolled, double-blind clinical trial to evaluate the efficacy and safety of ginseng polysaccharide (Y-75). J Transl Med 2014;12:283.
  39. 39. Khazdair MR. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol 2015;2015:841823.
  40. 40. Noor NA, Fahmy HM, Mohammed FF, Elsayed AA, Radwan NM. Nigella sativa ameliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. Int J Clin Exp Pathol 2015;8:6269–86.
  41. 41. Fahmy H, Noor NA, Mohammed FF, Elsayed AA, Radwan NM. Nigella sativa as an anti-inflammatory and promising remyelinating agent in the cortex and hippocampus of experimental autoimmune encephalomyelitis-induced rats. J Basic Appl Zool 2014;67:182–95.
  42. 42. Chandrasekaran VR, Hsu DZ, Liu MY. Beneficial effect of sesame oil on heavy metal toxicity. JPEN J Parenter Enteral Nutr 2014;38:179–85.
  43. 43. Ghazavi A, Mosayebi G. The mechanism of sesame oil in ameliorating experimental autoimmune encephalomyelitis in C57BL/6 mice. Phytother Res 2012;26:34–8.
  44. 44. Mosayebi G, Ghazavi A, Salehi H, Payani MA, Khazae MR. Effect of sesame oil on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mice. Pak J Biol Sci 2007;10:1790–6.
  45. 45. Wang Y, Kasper LH. The role of microbiome in central nervous system disorders. Brain Behav Immun 2014;38:1–12
  46. 46. Kobayashi T, Kato I, Nanno M, Shida K, Shibuya K, Matsuoka Y, Onoue M. Oral administration of probiotic bacteria, Lactobacillus casei and Bifidobacterium breve, does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis. Immunopharmacol Immunotoxicol 2010;32:116–24.
  47. 47. Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Westrom B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One 2010;5:e9009.
  48. 48. Maassen CB, Claassen E. Strain-dependent effects of probiotic lactobacilli on EAE autoimmunity. Vaccine 2008;26: 2056-7
  49. 49. Khodaie L, Sadeghpoor O. Ginger from ancient times to the new outlook. Jundishapur J Nat Pharm Prod 2015;10:e18402.
  50. 50. Jafarzadeh A, Mohammadi-Kordkhayli M, Ahangar-Parvin R, Azizi V, Khoramdel-Azad H, Shamsizadeh A, Ayoobi A, Nemati M, Hassan Z, Moazeni S. Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease. J Neuroimmunol 2014;276:80–8
  51. 51. Mirshafiey A. Venom therapy in multiple sclerosis. Neuropharmacology 2007;53:353–61.
  52. 52. Karimi A, Parivar K, Nabiuni M, Haghighi S, Imani S, Afrouzi H. Effect of honey bee venom on Lewis rats with experimental allergic encephalomyelitis as regards changes of GABA and glutamate. Iran J Pharm Res 2011;7:295–300.
  53. 53. Yunes Quartino PJ, Pusterla JM, Galvan Josa VM, Fidelio GD, Oliveira RG. CNS myelin structural modification induced in vitro by phospholipases A2. Biochim Biophys Acta 2016;1858:123–9.
  54. 54. Wesselius T, Heersema DJ, Mostert JP, Heerings M, Admiraal Behloul F, Talebian A, van Buchem MA, De Keyser J. A randomized crossover study of bee sting therapy for multiple sclerosis. Neurology 2005;65:1764–8.
  55. 55. Castro HJ, Mendez-Lnocencio JI, Omidvar B, Omidvar J, Santilli J, Nielsen Jr HS, Pavot AP, Richert JR, Bellanti JA. A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis. Allergy Asthma Proc 2005;26:470–6.
  56. 56. Shukitt-Hale B. Blueberries and neuronal aging. Gerontology 2012;58:518–23.
  57. 57. Xin J, Feinstein DL, Hejna MJ, Lorens SA, McGuire SO. Beneficial effects of blueberries in experimental autoimmune encephalomyelitis. J Agric Food Chem 2012;60:574
  58. 58. Multiple Sclerosis: Current Status and Strategies for the Future [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK222385/