Download PDF
Semin Neurol 2003; 23(2): 121-132
DOI: 10.1055/s-2003-41139
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Basic Principles of Immunotherapy for Neurologic Diseases

Reinhard Hohlfeld1 , Marinos C. Dalakas2
  • 1Institute for Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany
  • 2Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
Further Information

Publication History

Publication Date:
01 August 2003 (online)

    Permissions and Reprints

ABSTRACT

Immunosuppressive drugs and immunomodulating procedures can improve the quality of life in patients with immune-related neurologic diseases and can even be lifesaving if properly used to avoid deleterious or irreversible adverse effects. For the successful use of these drugs or procedures, the treating physician must be familiar and comfortable with the drugs' mode of action, the accuracy of the diagnosis, the goals and expectations of therapy, and the risk-benefit ratio of the therapy. Improvement must be based on a beneficial change in activities of daily living and not solely on a change in the laboratory test values.

KEYWORDS

Immunomodulation - neuroimmunological diseases - immunosuppressive therapy

REFERENCES

  • 1 Moalem G, Gdalyahu A, Shani Y. et al . Production of neurotrophins by activated T cells: implications for neurotrophic autoimmunity.  J Autoimmun . 2000;  15 331-345
    CrossrefPubMedGoogle Scholar
  • 2 Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H. The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis.  J Neuroimmunol . 2000;  107 161-166
    CrossrefPubMedGoogle Scholar
  • 3 Kerschensteiner M, Gallmeier E, Behrens L. et al . Activated human T cells, B cells and monocytes produce brain-derived neurotrophic factor (BDNF) in vitro and in brain lesions: a neuroprotective role of inflammation?.  J Exp Med . 1999;  189 865-870
    CrossrefPubMedGoogle Scholar
  • 4 Dalakas M C. Neuroimmunotherapy: a practical approach to the treatment of immune-mediated neurologic diseases.  Sem Neurol . 1994;  14 97-105
    PubMedGoogle Scholar
  • 5 Dalakas M C. Immunotherapies in the treatment of neuromuscular diseases. In: Katirji B, Kaminski HJ, Preston DC, Ruff RL, Shapiro BE, eds. Neuromuscular Disorders in Clinical Practice Woburn, MA: Butterworth-Heineman 2002 : 364-383
    Google Scholar
  • 6 Peterson E J, Koretsky G A. Signal transduction in T lymphocytes.  Clin Exp Rheumatol . 1999;  17 107-114
    PubMedGoogle Scholar
  • 7 Halloran P F. Sirolimus and cyclosporin for renal transplantation.  Lancet . 2000;  356 179-180
    CrossrefPubMedGoogle Scholar
  • 8 Miller D H, Khan O A, Sheremata W A. et al . A controlled trial of Natalizumab for relapsing multiple sclerosis.  N Engl J Med . 2003;  348 15-23
    CrossrefPubMedGoogle Scholar
  • 9 Lipsky J J. Mycophenolate mofetil.  Lancet . 1996;  348 1357-1359
    CrossrefPubMedGoogle Scholar
  • 10 Chaudhry V, Cornblath D R, Griffin J W, O'Brien R, Drachman D B. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.  Neurology . 2001;  56 94-96
    CrossrefPubMedGoogle Scholar
  • 11 Ciafaloni E, Massey J M, Tucker-Lipscomb B, Sanders D B. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study.  Neurology . 2001;  56 97-99
    CrossrefPubMedGoogle Scholar
  • 12 Abraham R T. Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling.  Curr Opin Immunol . 1998;  10 330-336
    CrossrefPubMedGoogle Scholar
  • 13 Guo X, Dillman III F J, Dawson V L, Dawson T M. Neuroimmunophilins: novel neuroprotective and neuroregenerative targets.  Ann Neurol . 2001;  50 6-16
    CrossrefPubMedGoogle Scholar
  • 14 Drachman D B, Jones R J, Brodsky R A. Treatment of refractory myasthenia: "rebooting" with high-dose cyclophosphamide.  Ann Neurol . 2003;  53 29-34
    CrossrefPubMedGoogle Scholar
  • 15 Lewis R A, Lisak R P. "Rebooting" the immune system with cyclophosphamide: taking risks for a "cure"?.  Ann Neurol . 2003;  53 7-9
    CrossrefPubMedGoogle Scholar
  • 16 Hartung H P, Gonsette R, Konig N. et al . Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.  Lancet . 2002;  360 2018-2025
    CrossrefPubMedGoogle Scholar
  • 17 Jacobs L, Johnson K P. A brief history of the use of interferons as treatment of multiple sclerosis.  Arch Neurol . 1994;  51 1245-1251
    PubMedGoogle Scholar
  • 18 Panitch H S, Hirsch R L, Schindler J, Johnson K P. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system.  Neurology . 1987;  37 1097-1102
    PubMedGoogle Scholar
  • 19 Sibley W A, IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis I: clinical results of a multicenter, randomized, double-blind, placebo-controlled trial.  Neurology . 1993;  43 655-661
    PubMedGoogle Scholar
  • 20 IFNB Multiple Sclerosis Study Group. Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial.  Neurology . 1995;  45 1277-1285
    PubMedGoogle Scholar
  • 21 Jacobs L D, Cookfair D L, Rudick R A. et al . Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis.  Ann Neurol . 1996;  39 285-294
    CrossrefPubMedGoogle Scholar
  • 22 Ebers G C. PRISM (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis). Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis.  Lancet . 1998;  352 1498-1504
    CrossrefPubMedGoogle Scholar
  • 23 Kappos L. European Study Group on Interferon-beta in Secondary Progressive MS. Placebo-controlled multicenter randomized trial of interferon β-1b in treatment of secondary progressive multiple sclerosis.  Lancet . 1998;  352 1491-1497
    CrossrefPubMedGoogle Scholar
  • 24 Stone L A, Frank J A, Albert P S. et al . The effect of interferon-β on blood-brain barrier disruptions demonstrated by contrast-enhanced magnetic resonance imaging in relapsing-remitting multiple sclerosis.  Ann Neurol . 1995;  37 611-619
    CrossrefPubMedGoogle Scholar
  • 25 Walther E U, Hohlfeld R. Multiple sclerosis: side effects of interferon beta therapy and their management.  Neurology . 1999;  53 1622-1627
    CrossrefPubMedGoogle Scholar
  • 26 Dayal A S, Jensen M A, Lledo A, Arnason B GW. Interferon-gamma secreting cells in multiple sclerosis patients treated with interferon beta-1b.  Neurology . 1995;  45 2173-2177
    PubMedGoogle Scholar
  • 27 Brod S A, Marshall G D, Henninger E M, Sriram S, Khan M, Wolinsky J S. Interferon-β1b treatment decreases tumor necrosis factor-α and increases interleukin-6 production in multiple sclerosis.  Neurology . 1996;  46 1633-1638
    PubMedGoogle Scholar
  • 28 IFNB Multiple Sclerosis Study Group, UBC MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years.  Neurology . 1996;  47 889-894
    PubMedGoogle Scholar
  • 29 Khan O A, Dhib-Jalbut S S. Neutralizing antibodies to interferon β-1a and interferon β-1b in MS patients are cross-reactive.  Neurology . 1998;  51 1698-1702
    PubMedGoogle Scholar
  • 30 Yong V W, Chabot S, Stüve O, Williams G. Interferon-β in the treatment of multiple sclerosis: mechanisms of action.  Neurology . 1998;  51 682-689
    PubMedGoogle Scholar
  • 31 Rudick R A, Simonian N A, Alam J A. et al . Incidence and significance of neutralizing antibodies to interferon beta-1a in multiple sclerosis.  Neurology . 1998;  50 1266-1272
    PubMedGoogle Scholar
  • 32 Bertolotto A, Malucchi S, Sala A. et al . Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory.  J Neurol Neurosurg Psychiatry . 2002;  73 148-153
    CrossrefPubMedGoogle Scholar
  • 33 Arnon R, Sela M, Teitelbaum D. New insights into the mechanism of action of copolymer 1 in experimental allergic encephalomyelitis and multiple sclerosis.  J Neurol . 1996;  243 (suppl 1) S8-S13
    PubMedGoogle Scholar
  • 34 Neuhaus O, Farina C, Yassouridis A. et al . Multiple sclerosis: comparison of copolymer-I reactive T cell lines from treated and untreated subjects reveals cytokine shift from TH1 to TH2.  Proc Natl Acad Sci U S A . 2000;  97 7452-7457
    PubMedGoogle Scholar
  • 35 Wekerle H, Linington C, Lassmann H, Meyermann R. Cellular immune reactivity within the CNS.  Trends Neurosci . 1986;  9 271-277
    CrossrefPubMedGoogle Scholar
  • 36 Neuhaus O, Farina C, Wekerle H, Hohlfeld R. Mechanisms of action of glatiramer acetate in multiple sclerosis.  Neurology . 2001;  56 702-706
    PubMedGoogle Scholar
  • 37 Ziemssen T, Kümpfel T, Klinkert W EF, Neuhaus O, Hohlfeld R. Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy.  Brain . 2002;  125 2381-2391
    CrossrefPubMedGoogle Scholar
  • 38 Dalakas M C. Intravenous immune globulin therapy for neurologic diseases.  Ann Intern Med . 1997;  126 721-730
    CrossrefPubMedGoogle Scholar
  • 39 Kazatchkine M D, Kaveri S V. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin.  N Engl J Med . 2001;  345 747-755
    CrossrefPubMedGoogle Scholar
  • 40 Hohlfeld R, Melms A, Schneider C, Toyka K V, Drachman D B. Therapy for myasthenia gravis and myasthenic syndromes. In: Brandt T, Caplan LR, Dichgans J, Diener HC, Kennard C, eds. Neurological Disorders: Course and Treatment 2nd ed. San Diego: Academic Press 2003: 1341-1362
    Google Scholar
  • 41 Yeh J H, Chiu H C. Comparison between double-filtration plasmapheresis and immunoadsorption plasmapheresis in the treatment of patients with myasthenia gravis.  J Neurol . 2000;  247 510-513
    CrossrefPubMedGoogle Scholar
  • 42 Gronseth G S, Barohn R J. Thymectomy for Myasthenia Gravis.  Curr Treat Options Neurol . 2002;  4 203-209
    CrossrefPubMedGoogle Scholar
  • 43 Lanska D J. Indications for thymectomy in myasthenia gravis.  Neurology . 1990;  40 1828-1829
    CrossrefPubMedGoogle Scholar
  • 44 Evoli A, Minisci C, Di Schino C. et al . Thymoma in patients with MG: characteristics and long-term outcome.  Neurology . 2002;  59 1844-1850
    PubMedGoogle Scholar
  • 45 Comi G, Kappos L, Clanet M. et al . Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.  J Neurol . 2000;  247 376-382
    CrossrefPubMedGoogle Scholar
  • 46 Hohlfeld R. How promising is hematopoetic stem cell transplantation in multiple sclerosis?.  J Neurol . 2002;  249 1147-1149
    PubMedGoogle Scholar
  • 47 Compston A, Ebers G, Lassmann H, McDonald W I, Matthews B, Wekerle H. McAlpine's Multiple Sclerosis 3rd ed.  London: Churchill Livingstone 1998
    Google Scholar
  • 48 Weilbach F X, Gold R. Disease modifying treatments for multiple sclerosis: what is the horizon?.  CNS Drugs . 1999;  11 133-157
    PubMedGoogle Scholar
  • 49 Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis: principles, problems and perspectives.  Brain . 1997;  120 865-916
    CrossrefPubMedGoogle Scholar
  • 50 Martin R, Sturzebecher C S, McFarland H F. Immunotherapy of multiple sclerosis: where are we?.  <~>Where should we go? Nat Immunol . 2001;  2 785-788
    PubMedGoogle Scholar
  • 51 Krummel M F, Davis M M. Dynamics of the immunological synapse: finding, establishing and solidifying a connection.  Curr Opin Immunol . 2002;  14 66-74
    CrossrefPubMedGoogle Scholar
  • 52 Gold R, Dalakas M C, Toyka K V. Immunotherapy in autoimmune neuromuscular disorders.  Lancet Neurol . 2003;  2 22-32
    CrossrefPubMedGoogle Scholar
      >