Advertisement

Biotherapy in Inflammatory Diseases of the CNS: Current Knowledge and Applications

  • Nicolas Collongues
  • Laure Michel
  • Jérôme de Seze
Multiple Sclerosis and Related Disorders (P Villoslada, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Multiple Sclerosis and Related Disorders

Opinion statement

Biotherapy represents an innovative therapeutic approach that includes immunotherapy (vaccines, apheresis, and antibodies); gene therapy; and stem cell transplants. Their development helps to cross the bridge from bench to bedside and brings new hope of a cure for severe diseases in different fields of medicine. In neurology, a growing range of applications is being developed for these medications. Valuable results are now available in the field of autoimmunity, neuro-oncology, paraneoplastic manifestations, and neurodegenerative disorders. In this review, we examine the current and future applications of biotherapy in the field of inflammation of the central nervous system. We demonstrate its contribution in clinical practice, where it has enabled a significant level of effectiveness to be achieved. Indeed, the efficacy of these new biodrugs provides a solution for patients refractory to standard therapies, such as intravenous immunoglobulins in limbic encephalitis, plasma exchanges in neuromyelitis optica and anti-CD20 monoclonal antibodies in multiple sclerosis. They also mark the first steps towards individualized medicine.

Keywords

Biotherapy Monoclonal antibody Stem cell Gene therapy 

Notes

Compliance with Ethical Standard

Conflict of Interest

Nicolas Collongues has received board membership fees, honoraria, and paid travel accommodations from Biogen, Merck, Novartis, and Sanofi. Laure Michel has received honoraria payments from Genzyme and Roche and paid travel accommodations from Novartis. Jérôme de Seze has received board membership fees from Biogen, Genzyme, Teva, Merck, Novartis, and Roche.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gretch D. Editorial commentary: advocating the concept of GB virus C biotherapy against AIDS. Clin Infect Dis:Off Publ Infect Dis Soc Am. 2012;55(7):1020–1.CrossRefGoogle Scholar
  2. 2.
    Naji A, Rouas-Freiss N, Durrbach A, Carosella ED, Sensebe L, Deschaseaux F. Concise review: combining human leukocyte antigen G and mesenchymal stem cells for immunosuppressant biotherapy. Stem Cells. 2013;31(11):2296–303.CrossRefPubMedGoogle Scholar
  3. 3.
    Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature. 2001;411(6835):380–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Thorne SH, Negrin RS, Contag CH. Synergistic antitumor effects of immune cell-viral biotherapy. Science. 2006;311(5768):1780–4.CrossRefPubMedGoogle Scholar
  5. 5.
    van Rooij E, Olson EN. MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat Rev Drug Discov. 2012;11(11):860–72.CrossRefPubMedGoogle Scholar
  6. 6.
    LEEM. Etude biomédicaments. wwwleemorg. 2015.Google Scholar
  7. 7.
    Niidome T, Huang L. Gene therapy progress and prospects: nonviral vectors. Gene Ther. 2002;9(24):1647–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008;451(7181):937–42.CrossRefPubMedGoogle Scholar
  9. 9.
    Lunemann JD, Nimmerjahn F, Dalakas MC. Intravenous immunoglobulin in neurology—mode of action and clinical efficacy. Nat Rev Neurol. 2015;11(2):80–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Lunemann JD, Quast I, Dalakas MC. Efficacy of intravenous immunoglobulin in neurological diseases. Neurotherapeutics: J Am Soc Exp NeuroTher. 2015.Google Scholar
  11. 11.
    Hommes OR, Sorensen PS, Fazekas F, Enriquez MM, Koelmel HW, Fernandez O, et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet. 2004;364(9440):1149–56.CrossRefPubMedGoogle Scholar
  12. 12.
    Pohlau D, Przuntek H, Sailer M, Bethke F, Koehler J, Konig N, et al. Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study. Mult Scler. 2007;13(9):1107–17.CrossRefPubMedGoogle Scholar
  13. 13.
    Achiron A, Kishner I, Dolev M, Stern Y, Dulitzky M, Schiff E, et al. Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis. J Neurol. 2004;251(9):1133–7.CrossRefPubMedGoogle Scholar
  14. 14.
    Haas J, Maas-Enriquez M, Hartung HP. Intravenous immunoglobulins in the treatment of relapsing remitting multiple sclerosis—results of a retrospective multicenter observational study over five years. Mult Scler. 2005;11(5):562–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Fragoso YD, Adoni T, Alves-Leon SV, Azambuja Jr ND, Barreira AA, Brooks JB, et al. Postpartum treatment with immunoglobulin does not prevent relapses of multiple sclerosis in the mother. Health Care Women Int. 2015;36(10):1072–80.CrossRefPubMedGoogle Scholar
  16. 16.
    Bien CG, Granata T, Antozzi C, Cross JH, Dulac O, Kurthen M, et al. Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement. Brain. 2005;128(Pt 3):454–71.CrossRefPubMedGoogle Scholar
  17. 17.
    Tenembaum S, Chitnis T, Nakashima I, Collongues N, McKeon A, Levy M, et al. Neuromyelitis optica spectrum disorders in children and adolescents. Neurology. 2016;87(9 Suppl 2):S59–66.CrossRefPubMedGoogle Scholar
  18. 18.
    Gastaldi M, Thouin A, Vincent A. Antibody-mediated autoimmune encephalopathies and immunotherapies. Neurotherapeutics: J Am Soc Exp NeuroThe. 2016;13(1):147–62.CrossRefGoogle Scholar
  19. 19.
    Pohl D, Alper G, Van Haren K, Kornberg AJ, Lucchinetti CF, Tenembaum S, et al. Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology. 2016;87(9 Suppl 2):S38–45.CrossRefPubMedGoogle Scholar
  20. 20.
    Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol. 2006;6(4):535–42.CrossRefPubMedGoogle Scholar
  22. 22.
    McDaneld LM, Fields JD, Bourdette DN, Bhardwaj A. Immunomodulatory therapies in neurologic critical care. Neurocrit Care. 2010;12(1):132–43.CrossRefPubMedGoogle Scholar
  23. 23.
    Gwathmey K, Balogun RA, Burns T. Neurologic indications for therapeutic plasma exchange: 2013 update. J Clin Apheresis. 2014;29(4):211–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Miyamoto K, Kusunoki S. Intermittent plasmapheresis prevents recurrence in neuromyelitis optica. Ther Apher Dial. 2009;13(6):505–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Granata T, Fusco L, Gobbi G, Freri E, Ragona F, Broggi G, et al. Experience with immunomodulatory treatments in Rasmussen’s encephalitis. Neurology. 2003;61(12):1807–10.CrossRefPubMedGoogle Scholar
  26. 26.
    Kobayashi M, Nanri K, Taguchi T, Ishiko T, Yoshida M, Yoshikawa N, et al. Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase. J Clin Apher. 2015;30(1):43–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Kleiter I, Gahlen A, Borisow N, Fischer K, Wernecke KD, Wegner B, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206–16.CrossRefPubMedGoogle Scholar
  28. 28.
    • Beck A, Wurch T, Bailly C, Corvaia N. Strategies and challenges for the next generation of therapeutic antibodies. Nat Rev Immunol. 2010;10(5):345–52. This review discusses the history and development of monoclonal antibodies. Innovations for optimizing the structure of IgG antibodies and for choosing the best therapeutic antigens are mentionedCrossRefPubMedGoogle Scholar
  29. 29.
    Lampson LA. Monoclonal antibodies in neuro-oncology: getting past the blood-brain barrier. MAbs. 2011;3(2):153–60.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Scheen AJ. International classification of various types of monoclonal antibodies. Revue medicale de Liege. 2009;64(5–6):244–7.PubMedGoogle Scholar
  31. 31.
    Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910.CrossRefPubMedGoogle Scholar
  32. 32.
    Rudick RA, Stuart WH, Calabresi PA, Confavreux C, Galetta SL, Radue EW, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):911–23.CrossRefPubMedGoogle Scholar
  33. 33.
    Havrdova E, Galetta S, Hutchinson M, Stefoski D, Bates D, Polman CH, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab safety and efficacy in relapsing-remitting multiple sclerosis (AFFIRM) study. Lancet Neurol. 2009;8(3):254–60.CrossRefPubMedGoogle Scholar
  34. 34.
    Krumbholz M, Meinl I, Kumpfel T, Hohlfeld R, Meinl E. Natalizumab disproportionately increases circulating pre-B and B cells in multiple sclerosis. Neurology. 2008;71(17):1350–4.CrossRefPubMedGoogle Scholar
  35. 35.
    Stuve O, Marra CM, Bar-Or A, Niino M, Cravens PD, Cepok S, et al. Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. Arch Neurol. 2006;63(10):1383–7.CrossRefPubMedGoogle Scholar
  36. 36.
    Vermersch P, Kappos L, Gold R, Foley JF, Olsson T, Cadavid D, et al. Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology. 2011;76(20):1697–704.CrossRefPubMedGoogle Scholar
  37. 37.
    Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870–80.CrossRefPubMedGoogle Scholar
  38. 38.
    • Plavina T, Subramanyam M, Bloomgren G, Richman S, Pace A, Lee S, et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol. 2014;76(6):802–12. This article illustrates the management of risk related to the use of natalizumab. This is an exemplary study showing the necessity to frame the use of monoclonal antibodies in a perspective of personalized medicineCrossRefPubMedGoogle Scholar
  39. 39.
    Schwab N, Schneider-Hohendorf T, Posevitz V, Breuer J, Gobel K, Windhagen S, et al. L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients. Neurology. 2013;81(10):865–71.CrossRefPubMedGoogle Scholar
  40. 40.
    Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–28.CrossRefPubMedGoogle Scholar
  41. 41.
    Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39.CrossRefPubMedGoogle Scholar
  42. 42.
    Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann Neurol. 1999;46(3):296–304.CrossRefPubMedGoogle Scholar
  43. 43.
    Daikeler T, Labopin M, Di Gioia M, Abinun M, Alexander T, Miniati I, et al. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT autoimmune disease working party. Blood. 2011;118(6):1693–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Boye J, Elter T, Engert A. An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab. Ann Oncol: Off J Eur Soc Med Oncol/ESMO. 2003;14(4):520–35.CrossRefGoogle Scholar
  45. 45.
    Collongues N, de Seze J. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica. Ther Adv Neurol Disord. 2016;9(3):180–8.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358(7):676–88.CrossRefPubMedGoogle Scholar
  47. 47.
    Hawker K, O’Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66(4):460–71.CrossRefPubMedGoogle Scholar
  48. 48.
    Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010;62(1):222–33.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the lupus nephritis assessment with rituximab study. Arthritis Rheum. 2012;64(4):1215–26.CrossRefPubMedGoogle Scholar
  50. 50.
    Oon S, Wilson NJ, Wicks I. Targeted therapeutics in SLE: emerging strategies to modulate the interferon pathway. Clin Transl Immunology. 2016;5(5):e79.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Collongues N, Brassat D, Maillart E, Labauge P, Ouallet JC, Carra-Dalliere C, et al. Efficacy of rituximab in refractory neuromyelitis optica. Multiple sclerosis. 2015.Google Scholar
  52. 52.
    Zaheer F, Berger JR. Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps. Therapeutic advances in drug safety. 2012;3(5):227–39.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378(9805):1779–87.CrossRefPubMedGoogle Scholar
  54. 54.
    Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34.CrossRefPubMedGoogle Scholar
  55. 55.
    Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.CrossRefPubMedGoogle Scholar
  56. 56.
    Mysler EF, Spindler AJ, Guzman R, Bijl M, Jayne D, Furie RA, et al. Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study. Arthritis Rheum. 2013;65(9):2368–79.CrossRefPubMedGoogle Scholar
  57. 57.
    Teeling JL, Mackus WJ, Wiegman LJ, van den Brakel JH, Beers SA, French RR, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006;177(1):362–71.CrossRefPubMedGoogle Scholar
  58. 58.
    Barth MJ, Mavis C, Czuczman MS, Hernandez-Ilizaliturri FJ. Ofatumumab exhibits enhanced in vitro and in vivo activity compared to rituximab in pre-clinical models of mantle cell lymphoma. Clin Cancer Res: Off J Am Assoc Cancer Res. 2015.Google Scholar
  59. 59.
    Bologna L, Gotti E, Da Roit F, Intermesoli T, Rambaldi A, Introna M, et al. Ofatumumab is more efficient than rituximab in lysing B chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy. J Immunol. 2013;190(1):231–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Wierda WG, Padmanabhan S, Chan GW, Gupta IV, Lisby S, Osterborg A, et al. Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study. Blood. 2011;118(19):5126–9.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Sorensen PS, Lisby S, Grove R, Derosier F, Shackelford S, Havrdova E, et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology. 2014;82(7):573–81.CrossRefPubMedGoogle Scholar
  62. 62.
    Sheridan JP, Zhang Y, Riester K, Tang MT, Efros L, Shi J, et al. Intermediate-affinity interleukin-2 receptor expression predicts CD56 (bright) natural killer cell expansion after daclizumab treatment in the CHOICE study of patients with multiple sclerosis. Mult Scler. 2011;17(12):1441–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): A randomised, double-blind, placebo-controlled trial. Lancet. 2013;381(9884):2167–75.CrossRefPubMedGoogle Scholar
  64. 64.
    Kappos L, Wiendl H, Selmaj K, Arnold DL, Havrdova E, Boyko A, et al. Daclizumab HYP versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2015;373(15):1418–28.CrossRefPubMedGoogle Scholar
  65. 65.
    Furie R, Petri M, Zamani O, Cervera R, Wallace DJ, Tegzova D, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3918–30.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Navarra SV, Guzman RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: A randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721–31.CrossRefPubMedGoogle Scholar
  67. 67.
    Kalunian KC, Merrill JT, Maciuca R, McBride JM, Townsend MJ, Wei X, et al. A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. 2016;75(1):196–202.CrossRefPubMedGoogle Scholar
  68. 68.
    Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, et al. Anifrolumab, an anti-interferon-alpha receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol. 2017;69(2):376–86.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Borba HH, Funke A, Wiens A, Utiyama SR, Perlin CM, Pontarolo R. Update on biologic therapies for systemic lupus erythematosus. Curr Rheumatol Rep. 2016;18(7):44.CrossRefPubMedGoogle Scholar
  70. 70.
    Havrdova E, Belova A, Goloborodko A, Tisserant A, Wright A, Wallstroem E, et al. Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study. J Neurol. 2016;263(7):1287–95.CrossRefPubMedGoogle Scholar
  71. 71.
    Ringelstein M, Ayzenberg I, Harmel J, Lauenstein AS, Lensch E, Stogbauer F, et al. Long-term therapy with interleukin 6 receptor blockade in highly active neuromyelitis optica spectrum disorder. JAMA Neurol. 2015;72(7):756–63.CrossRefPubMedGoogle Scholar
  72. 72.
    Pittock SJ, Lennon VA, McKeon A, Mandrekar J, Weinshenker BG, Lucchinetti CF, et al. Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: an open-label pilot study. Lancet Neurol. 2013;12(6):554–62.CrossRefPubMedGoogle Scholar
  73. 73.
    •• Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663–76. This paper demonstrates that differentiated cells can be reprogrammed to an embryonic-like state in mouse. This paper opens the way to a new generation of gene therapiesCrossRefPubMedGoogle Scholar
  74. 74.
    Sola-Valls N, Sepulveda M, Blanco Y, Saiz A. Current role of chemotherapy and bone marrow transplantation in multiple sclerosis. Curr Treat Options Neurol. 2015;17(1):324.CrossRefPubMedGoogle Scholar
  75. 75.
    Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388(10044):576–85.CrossRefPubMedGoogle Scholar
  76. 76.
    Reston JT, Uhl S, Treadwell JR, Nash RA, Schoelles K. Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review. Mult Scler. 2011;17(2):204–13.CrossRefPubMedGoogle Scholar
  77. 77.
    Sormani MP, Muraro P. Updated views on autologous hematopoietic stem cell transplantation for treatment of multiple sclerosis. Expert Rev Neurother. 2016;16(5):469–70.CrossRefPubMedGoogle Scholar
  78. 78.
    Atkins HL, Freedman MS. Hematopoietic stem cell therapy for multiple sclerosis: top 10 lessons learned. Neurotherapeutics: J Am Soc Exp NeuroTher. 2013;10(1):68–76.CrossRefGoogle Scholar
  79. 79.
    Tyndall A, van Laar JM. Stem cell transplantation and mesenchymal cells to treat autoimmune diseases. Presse Med. 2016;45(6 Pt 2):e159–69.CrossRefPubMedGoogle Scholar
  80. 80.
    Yamout B, Hourani R, Salti H, Barada W, El-Hajj T, Al-Kutoubi A, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010;227(1–2):185–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, et al. Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med. 2009;7:29.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, Alimoghaddom K, Talebian F, Hooshmand F, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol. 2007;4(1):50–7.PubMedGoogle Scholar
  83. 83.
    Liang J, Zhang H, Hua B, Wang H, Wang J, Han Z, et al. Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler. 2009;15(5):644–6.CrossRefPubMedGoogle Scholar
  84. 84.
    Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012;11(2):150–6.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Llufriu S, Sepulveda M, Blanco Y, Marin P, Moreno B, Berenguer J, et al. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis. PLoS One. 2014;9(12):e113936.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    • Maguire CA, Ramirez SH, Merkel SF, Sena-Esteves M, Breakefield XO. Gene therapy for the nervous system: challenges and new strategies. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. 2014;11(4):817–39. This review makes a state of the art in the field of gene therapy. Advantages, limitations, and applications of gene therapy in neurology are largely and accurately discussedCrossRefGoogle Scholar
  87. 87.
    Bordignon C, Mavilio F, Ferrari G, Servida P, Ugazio AG, Notarangelo LD, et al. Transfer of the ADA gene into bone marrow cells and peripheral blood lymphocytes for the treatment of patients affected by ADA-deficient SCID. Hum Gene Ther. 1993;4(4):513–20.CrossRefPubMedGoogle Scholar
  88. 88.
    Grace PM, Loram LC, Christianson JP, Strand KA, Flyer-Adams JG, Penzkover KR, et al. Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy. Brain Behav Immun. 2016.Google Scholar
  89. 89.
    Sloane E, Ledeboer A, Seibert W, Coats B, van Strien M, Maier SF, et al. Anti-inflammatory cytokine gene therapy decreases sensory and motor dysfunction in experimental multiple sclerosis: MOG-EAE behavioral and anatomical symptom treatment with cytokine gene therapy. Brain Behav Immun. 2009;23(1):92–100.CrossRefPubMedGoogle Scholar
  90. 90.
    Ryu CH, Park KY, Hou Y, Jeong CH, Kim SM, Jeun SS. Gene therapy of multiple sclerosis using interferon beta-secreting human bone marrow mesenchymal stem cells. Biomed Res Int. 2013;2013:696738.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Lobell A, Weissert R, Storch MK, Svanholm C, de Graaf KL, Lassmann H, et al. Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc of immunoglobulin G suppresses experimental autoimmune encephalomyelitis. J Exp Med. 1998;187(9):1543–8.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Bar-Or A, Vollmer T, Antel J, Arnold DL, Bodner CA, Campagnolo D, et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch Neurol. 2007;64(10):1407–15.CrossRefPubMedGoogle Scholar
  93. 93.
    Garren H, Robinson WH, Krasulova E, Havrdova E, Nadj C, Selmaj K, et al. Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis. Ann Neurol. 2008;63(5):611–20.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Département de NeurologieCHU de StrasbourgStrasbourgFrance
  2. 2.Centre d′investigation cliniqueINSERMStrasbourgFrance
  3. 3.Département de neurologieCHU de NantesNantesFrance

Personalised recommendations