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Future Therapies for Multiple Sclerosis

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Multiple Sclerosis

Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

Future immunotherapy for immune-mediated neurologic diseases is in a state of rapid development. The current therapeutic arsenal consists of a mixture of older and new agents whose uses are actively being redefined. Our current understanding of mechanisms of action of established medications and developing approaches will be discussed in relation to disease pathogenesis models. Also, we will present a framework for incorporating current and future therapies into rational treatment strategies and will be addressed together with a review of relevant clinical studies. Mechanisms of immunotherapy and clinical strategies will be discussed in the context of multiple sclerosis (MS).

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References

  1. Steinman L, Lindsey JW, Alters S, Hodgkinson S. From treatment of experimental allergic encephalomyelitis to clinical trials in multiple sclerosis. In: Bach JF, ed., Monoclonal Antibodies and Peptide Therapy in Autoimmune Diseases. Marcel Dekker Inc., New York, 1993, pp. 253–260.

    Google Scholar 

  2. Brocke S, Gaur A, Piercy C, et al. Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen. Nature 1993;365:642–644.

    Article  PubMed  CAS  Google Scholar 

  3. Friedman A, Weiner HL. Induction of anergy or active suppression following oral tolerance is determined by frequency of feeding and antigen dosage. PNAS 1994;in press.

    Google Scholar 

  4. Abbas A. Die and let live: eliminating dangerous lymphocytes. Cell 1996;84: 655–657.

    Article  PubMed  CAS  Google Scholar 

  5. Webb S, Morris C, Sprent J. Extrathymic tolerance of mature T-cells: Clonal elimination as a consequence of immunity. Cell 1990;63:1249–1256.

    Article  PubMed  CAS  Google Scholar 

  6. Chen Y, Inobe J, Marks R, Gonella P, Kuchroo VK, Weiner HL. Peripheral deletion of antigen reactive T-cells in oral tolerance. Nature 1995;376:177–180.

    Article  PubMed  CAS  Google Scholar 

  7. Kerlero de Rosbo N, Milo R, Lees MB, Burger D, Bernard CC, Be-Nun A. Reactivity to myelin antigens in multiple sclerosis. JCI 1993;92:2602–2608.

    PubMed  CAS  Google Scholar 

  8. Ben-Nun A, Wekerle H, Cohen IR. Vaccination against autoimmune encephalomyelitis using attenuated cells of a T lymphocyte line reactive against myelin basic protein. Nature 1981; 292:60–61.

    Article  PubMed  CAS  Google Scholar 

  9. Khoury SJ, Hancock WW, Weiner HL. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated wtih down-regulation of inflammatory cytokines and differential upregulation of TGF-β, IL-4 and PGE expression in the brain. J Exp Medicine 1992;46:1355–1364.

    Article  Google Scholar 

  10. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994;265: 1237–1240.

    Article  PubMed  CAS  Google Scholar 

  11. Nicholson L, Greer J, Sobel RA, Lees MB, Kuchroo VK. An altered peptide ligand mediates immune deviation and prevents EAE. Immunity 1995;3:397–405.

    Article  PubMed  CAS  Google Scholar 

  12. Brocke S, Gijbels K, Allegretta M, et al. Treatment of EAE with a peptide analogue of MBP. Nature 1996;379:343–346.

    Article  PubMed  CAS  Google Scholar 

  13. Racke MK, Martin R, McFarland H, Fritz RB. Copolymer-1-induced inhibition of antigen-specific T-cell activation: Interference with antigen presentation. J Neuroimmunol 1992;37:75–84.

    Article  PubMed  CAS  Google Scholar 

  14. Teitelbaum D, Milo R, Arnon R, Sela M. Synthetic copolymer-1 inhibits human T-cell lines specific for myelin basic protein. PNAS 1992;89:137–141.

    Article  PubMed  CAS  Google Scholar 

  15. Teitelbaum D, Arnon R, Sela M. Immunodetection of experimental autoimune encehalomyelitis by oral administration of copolymer 1. Proc Natl Acad Sci USA 1999;96;3842–3847.

    Article  PubMed  CAS  Google Scholar 

  16. Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science 1989;246:668–670.

    Article  PubMed  CAS  Google Scholar 

  17. Vandenbark AA, Hashim G, Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature 1989;341:541–544.

    Article  PubMed  CAS  Google Scholar 

  18. Hafler DA. T Cell Vaccination in Multiple Sclerosis: A Preliminary Report. Clin Immunol Immunopathol 1992;62:307–313.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang J, Medaer R, Stinissen P, Hafler D, Raus J. MHC-restricted depletion of human myelin basic protein-reactive T cells by T cell vaccination. Science 1993;261:1451–1454.

    Article  PubMed  CAS  Google Scholar 

  20. Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of IL-2 responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med 1994;179:973–984.

    Article  PubMed  CAS  Google Scholar 

  21. Weiner HL, Friedman A, Miller A, et al. Oral Tolerance: Immunologic mechanisms and treatment of murine and human organ specific autoimmune diseases by oral administration of autoantigens. Ann Rev Immunol 1994;12: 809–837.

    Article  CAS  Google Scholar 

  22. Al-Sabbagh A, Miller A, Santos LM, Weiner HL. Suppression of PLP induced EAE in the SJL mouse by oral administration of MBP. Neurology 1994;24:2104–2109.

    CAS  Google Scholar 

  23. Al-Sabbagh A, Nelson PA, Weiner HL. Beta interferon enhances oral tolerance to MBP and PLP in experimental autoimmune encephalomyelitis. Neurology 1994;44:A242 (abstract)..

    Google Scholar 

  24. Arnason BGW. Interferon beta in multiple sclerosis. Neurology 1993;43:641–643.

    PubMed  CAS  Google Scholar 

  25. Hirsch RL, Panitch HS, Johnson KP. Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferon in vitro. J Clin Immunol 1985;5:386–389.

    Article  PubMed  CAS  Google Scholar 

  26. Noronha A, Toscas A, Jansen MA. IFN-β downregulates T cell activation and IFN-γ production: implications for MS. J Neuroimmunol 1993;46:145–153.

    Article  PubMed  CAS  Google Scholar 

  27. Antel JP, Brown-Bania M, Reder A, Cashman N. Activated suppressor cell dysfunction in multiple sclerosis. J Neuroimmunol 1986;137: 137–141.

    CAS  Google Scholar 

  28. Noronha A, Toscas A, Jensen MA. Interferon beta augments suppressor cell function in multiple sclerosis. Ann Neurol 1990;27:207–210.

    Article  PubMed  CAS  Google Scholar 

  29. Sibley WA, Bamford CR, Clark K. Clinical viral infections and multiple sclerosis. Lancet 1985;1: 1313–1315.

    Article  PubMed  CAS  Google Scholar 

  30. Smith D, Balshov K, et al. Increased IL-4 secretion and decreased gamma-IFN secretion in multiple sclerosis patients treated with cyclophosphamide or beta-interferon. The 9th International Congress of Immunology, San Francisco, California, July, 1995.

    Google Scholar 

  31. Rudick R, et al. In vitro and in vivo inhibition of mitogen driven T cell activation by recombinant interferon beta. Neurology 1993;43:2080–2087.

    PubMed  CAS  Google Scholar 

  32. Porrini A, Gambi D, Reder AT. Interferon effects on IL-10 secretion; mononuclear cell response to IL-10 is normal in multiple sclerosis patients. J Neuroimmunol 1995;61:27–34.

    Article  PubMed  CAS  Google Scholar 

  33. Soos JM, Mujtaba MG, Subramaniam PS, Streit WJ, Johnson HM. Oral feeding of interferon tau can prevent the acute and chronic relapsing forms of experimental allergic encephalomyelitis. J Neuroimmunol 1997;75: 43–50.

    Article  PubMed  CAS  Google Scholar 

  34. Olek MJ, Smith DR, Cook SL, Khoury SJ, Weiner HL. Phase I study of oral recombinant ovine interferon-tau in relapsing-remitting multiple sclerosis. AAN, Philadelphia, May 2001, S11.005.

    Google Scholar 

  35. Hafler DA, Weiner HL. In vivo labeling of peripheral blood T-cells using monoclonal antibodies: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol 1987;22:90–93.

    Article  Google Scholar 

  36. Yednock TA, Cannon C, Fritz L, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin. Nature 1992;356:63–66.

    Article  PubMed  CAS  Google Scholar 

  37. Archelos JJ, Jung S, Maurer M, et al. Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Ann Neurol 1993;34:145–154.

    Article  PubMed  CAS  Google Scholar 

  38. Hynes RO. Integrins: a family of cell surface receptors. Cell 1987; 48:549.

    Article  PubMed  CAS  Google Scholar 

  39. Frenette PS, Wagner DD. Adhesion molecules—Part 1. N Engl J Med 1996;334:1526–1529.

    Article  PubMed  CAS  Google Scholar 

  40. Frenette PS, Wagner DD. Adhesion molecules—Part II: Blood vessels and blood cells. N Engl J Med 1996;335:43–45.

    Article  PubMed  CAS  Google Scholar 

  41. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992;356:63–66

    Article  PubMed  CAS  Google Scholar 

  42. Kent SJ, Karlik SJ, Cannon C, et al. A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis. J Neuroimmunol 1995;58:1–10.

    Article  PubMed  CAS  Google Scholar 

  43. Kent SJ, Karlik SJ, Rice GP, Horner HC. A monoclonal antibody to alpha 4-integrin reverses the MR-detectable signs of experimental allergic encephalomyelitis in the guinea pig. J Magn Reson Imaging 1995;5:535–540.

    Article  PubMed  CAS  Google Scholar 

  44. Tubridy N, Behan PO, Capildeo R, et al. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology 1999;53:466–472.

    PubMed  CAS  Google Scholar 

  45. Miller DH, Khan OA, Sheremata WA, et al. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003;348:15–23.

    Article  PubMed  CAS  Google Scholar 

  46. Hafler DA, Fallis RJ, Dawson DM, Schlossman DF, Reinherz EL, Weiner HL. Immunologic responses of progressive multiple sclerosis patients treated with anti-T-cell monoclonal antibody. Neurology 1986;36:777–784.

    PubMed  CAS  Google Scholar 

  47. Hafler DA, Ritz J, Schlossman SF, Weiner HL. Anti-CD4 and anti-CD2 monoclonal antibodies infusions in humans: immunosuppressive effects and human anti-mouse responses. J Immunol 1988;141:131–138.

    PubMed  CAS  Google Scholar 

  48. Weinshenker BG, Bass B, Karlik S, Ebers GC, Rice GPA. An open trial of OKT3 in patients with multiple sclerosis. Neurology 1991;41:1047–1052.

    PubMed  CAS  Google Scholar 

  49. Lindsey J, Hodgkinson S, Mehta R, Mitchell D, Enzmann D, Steinman L. Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis. Ann Neurol 1994;36:183–189.

    Article  PubMed  CAS  Google Scholar 

  50. Barkhof, F, Thompson A, Hodgkinson S, et al. Double-blind, placebo-controlled, MR monitored exploratory trial of chimeric anti-CD4 antibodies in MS. The 11th European Congress on Multiple Sclerosis, Jerusalum, Israel, Sept. 1995.

    Google Scholar 

  51. Paolillo A, Coles AJ, Molyneux PD, et al. QuantitativeMRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology 1999;53:751–757.

    PubMed  CAS  Google Scholar 

  52. Killestein J, Olsson T, Wallstrom E, et al. Antibody-mediated suppression of Vbeta5.2/5.3+ T cells in multiple sclerosis: results from an MRI-monitored phase II clinical trial. Ann Neurol 2002;51:467–474.

    Article  PubMed  CAS  Google Scholar 

  53. Olsson T, Edenius C, Ferm M, et al. Depletion of Vbeta5.2/5.3 T cells with a humanized antibody in patients with multiple sclerosis. Eur J Neurol 2002;9:153–164.

    Article  PubMed  Google Scholar 

  54. Santambrogio L, Hochwald GM, Saxena B, et al. Studies on the mechanisms by which transforming growth factor-β (TGF-β) protects against allergic encephalomyelitis. J Immunol 1993; 151: 1116–1127.

    PubMed  CAS  Google Scholar 

  55. Rott O, Cash E, Fleischer B. Phosphokiesterase inhibitor pentoxifylline, a selective suppressor of T helper type 1-but not type 2-associated lymphokine production, prevents induction of experimental autoimmune encephalomyelitis in Lewis rats. Eur J Immunol 1993;23:1745–1751.

    Article  PubMed  CAS  Google Scholar 

  56. Elliot M, Maini R, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to TNF alpha. Arthritis Rheum 1993;36:1681–1690.

    Article  Google Scholar 

  57. Dwyer JM. Manipulating the immune system with immune globulin. N Engl J Med 1992;326:107–116.

    Article  PubMed  CAS  Google Scholar 

  58. Noseworthy JH, O’Brien PC, van Engelen BG, Rodriguez M. Intravenous immunoglobulin therapy in MS: progress from remyelination in the Theiler’s virus model to a randomized double blind placebo controlled clinical trial. J Neurol Neurosurg Psychiatry 1994;57:11–14

    Article  PubMed  Google Scholar 

  59. Sicotte NL, Liva SM, Klutch R, et al. Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 2002;52:421–428.

    Article  PubMed  CAS  Google Scholar 

  60. Neuhaus O, Strasser-Fuchs S, Fazekas F,et al. Statins as immunomodulators: comparison with interferon-beta 1b in MS. Neurology 2002;59:990–997.

    Article  PubMed  CAS  Google Scholar 

  61. Zamvil SS, Steinman L. Cholesterol-lowering statins possess anti-inflammatory activity that might be useful for treatment of MS. Neurology 2002;59:970–971.

    PubMed  Google Scholar 

  62. Cupps T, Edgar L, Fauci AS. Suppression of human B lymphocyte function by cyclophosphamide. J Immunol 1985;128:2453–2457.

    Google Scholar 

  63. Goodin DS, Arnason BG, Coyle PK, Frohman EM. The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003;61:1332.

    PubMed  CAS  Google Scholar 

  64. Scheinman R, Cogswell P, Lofquist AK, Baldwin AS Jr. Role of transcriptional activation of IKB alpha in mediation of immunosuppression by glucocorticoids. Science 1995;270:283–286.

    Article  PubMed  CAS  Google Scholar 

  65. Kupersmith MJ, Kaufman D, Paty DW, et al. Megadose corticosteroids in multiple sclerosis. Neurology 1994;44:1–4.

    PubMed  CAS  Google Scholar 

  66. Daynes R, Araneo B. Contrasting effects of glucocoricoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur J Immunol 1989;19: 2319–2325.

    Article  PubMed  CAS  Google Scholar 

  67. Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med 1992;326:581–588.

    Article  PubMed  CAS  Google Scholar 

  68. Beck RW, Cleary PA. Optic neuritis treatment trial: one-year follow-up results. Arch Ophthalmol 1993; 111:773–775.

    PubMed  CAS  Google Scholar 

  69. Zivadinov R, Rudick RA, De Masi R, et al. Effects of IVmethylprednisolone on brain atrophy in relapsing-remittingMS. Neurology 2001;57:1239–1247.

    PubMed  CAS  Google Scholar 

  70. Beck RW, Cleary PA, Trobe JD, et al. The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. N Engl J Med 1993;239:1764–1769.

    Article  Google Scholar 

  71. Cook SD, Devereux C, Troiano R, et al. Total lymphoid irradiation in multiple sclerosis. In: Rudick RA, Goodkin DE, eds., Treatment of multiple sclerosis: trial design, results, and future perspectives. Springer-Verlag, New York,1992, pp. 267–280.

    Google Scholar 

  72. Ahrens N, Salama A, Haas J. Mycophenolate-mofetil in the treatment of refractory multiple sclerosis. J Neurol 2001;248:713–714.

    Article  PubMed  CAS  Google Scholar 

  73. The Multiple Sclerosis Study Group. Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol 1990;27:591–605.

    Article  Google Scholar 

  74. Rudge P, Koetsier JC, Mertin J, et al. Randomized double blind controlled trial of cyclosporin in multiple sclerosis. J Neurol Neurosurg Psychiatry 1989;52:559–565.

    PubMed  CAS  Google Scholar 

  75. Hughes RA. Treatment of multiple sclerosis with azathioprine. In Goodkin DE, Rudick RA, eds., Treatment of multiple sclerosis: trial design, results, and future perspectives. Springer-Verlag, New York, 1992, pp.157–172.

    Google Scholar 

  76. Yudkin PL, Ellison GW, Ghezzi A, et al. Overview of azathioprine treatment in multiple sclerosis. Lancet 1991;338:1051–1055.

    Article  PubMed  CAS  Google Scholar 

  77. Goodkin D, Rudick R, VanderBrug MS. Low-dose (7.5mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. 1995;Ann Neurol 37:30–40.

    Article  PubMed  CAS  Google Scholar 

  78. Sipe JD, Romine J, Koziol JA, McMillan R, Zyroff J, Beutler E. Cladribine in the treatment of chronic progressive multiple sclerosis. Lancet 1994;344:9–13.

    Article  PubMed  CAS  Google Scholar 

  79. Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical andMRI outcomes of a multicenter controlledtrial. CladribineMRI Study Group. Neurology 2000;54:1145–1155.

    PubMed  CAS  Google Scholar 

  80. Filippi M, Rovaris M, Iannucci G, Mennea S, Sormani MP, Comi G. Whole brain volume changes in patients with progressiveMStreated with cladribine. Neurology 2000;55:1714–1718.

    PubMed  CAS  Google Scholar 

  81. Achiron A, Pras E, Gilad R, et al. Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis. Arch Neurol 1 9992;49:1233–1236.

    Google Scholar 

  82. Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 1997;349:589–593.

    Article  PubMed  CAS  Google Scholar 

  83. Noseworthy JH, O’Brien PC, Weinshenker BG, et al. IV immunoglobulin does not reverse established weakness in MS [In Process Citation]. Neurology 2000;55:1135–1143.

    PubMed  CAS  Google Scholar 

  84. Weinshenker BG, O’Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878–886.

    Article  PubMed  CAS  Google Scholar 

  85. van Gelder M, Kinwel-Bohre EP, van Bekkum DW. Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Trans 1993;11:233–241.

    Google Scholar 

  86. Burt RK, Burns W, Ruvolo P, et al. Syngeneic bone marrow transplantation eliminates V beta 8.2 T lymphocytes from the spinal cord of Lewis rats with experimental allergic encephalomyelitis. J Neurosci Res 1995;41: 526–531.

    Article  PubMed  CAS  Google Scholar 

  87. Nash RA, Bowen JD, McSweeney PA, et al. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. Blood 2003;102:2364–2372.

    Article  PubMed  CAS  Google Scholar 

  88. Burt RK, Cohen BA, Russell E, et al. Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores. Blood 2003;102:2373–2378.

    Article  PubMed  CAS  Google Scholar 

  89. Saiz A, Blanco Y, Carreras E, et al. Clinical and MRI outcome after autologous hematopoietic stem cell transplant in MS. Neurology 2004;62:282–284.

    PubMed  CAS  Google Scholar 

  90. Calabresi PA, Wilterdink JL, Rogg JM, Mills P, Webb A, Whartenby KA. An open-label trial of combination therapy with interferon beta-1a and oral methotrexate in MS. Neurology. 2002;58:314–317.

    PubMed  CAS  Google Scholar 

  91. Lublin FD, Baiere M, Cutter G, et al. Results of the extension of a trial to assess the long term safety of combining interferon beta-1a and glatiramer acetate. Neurology 58 2002;58:A85.

    Google Scholar 

  92. Kalkers NF, Barkhof F, Bergers E, van Schijndel R, Polman CH. The effect of the neuroprotective agent riluzole onMRI parameters in primary progressive multiple sclerosis: a pilot study. Mult Scler 2002;8: 532–533.

    Article  PubMed  CAS  Google Scholar 

  93. Paty DW. Magnetic resonance imaging in the assessment of disease activity in multiple sclerosis. Can J Neurol Sci 1988;15:266–272.

    PubMed  CAS  Google Scholar 

  94. McFarland HF, Frank JA, Albert PS, et al. Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis. Ann Neurol 1992;32: 758–766.

    Article  PubMed  CAS  Google Scholar 

  95. Khoury SJ, Guttmann CR, Orav EJ, et al. Longitudinal MRI imaging in multiple sclerosis: correlation between disability and lesion burden. Neurology 1994;44:2120–2124.

    PubMed  CAS  Google Scholar 

  96. Sharief MK, Hentges R. Association between tumor necrosis factor-α and disease progrssion in patients with mulitple sclerosis. NEngl J Med 1991;325: 467–472.

    Article  CAS  Google Scholar 

  97. Chofflon M, Juillard C, Julliard P, Gauthier G, Grau G. (1992). Tumor necrosis factor α production as a possible predictor of relapse in patients with multiple sclerosis. Eur Cytokine Net 1992;3: 523–531.

    CAS  Google Scholar 

  98. Rossman HS. Neutralizing antibodies to multiple sclerosis treatments.J Manag Care Pharm. 2004;10: S12–S19.

    PubMed  Google Scholar 

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  1. Multiple Sclerosis Center, Department of Neurology, University of California, Irvine, CA

    Michael J. Olek DO

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    Michael J. Olek DO

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Olek, M.J. (2005). Future Therapies for Multiple Sclerosis. In: Olek, M.J. (eds) Multiple Sclerosis. Current Clinical Neurology. Humana Press. https://doi.org/10.1385/1-59259-855-2:209

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