Review Article

Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

Author(s): Md. Asiful Islam*, Shoumik Kundu and Rosline Hassan

Volume 19, Issue 6, 2019

Page: [376 - 385] Pages: 10

DOI: 10.2174/1566523220666200306092556

Price: $65

Abstract

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.

Keywords: Gene therapy, multiple sclerosis, autoimmune disease, autoimmunity, demyelination, experimental autoimmune encephalitis, neurodegeneration.

Graphical Abstract

[1]
Keeler GD, Kumar S, Palaschak B, et al. Gene therapy-induced antigen-specific Tregs inhibit neuro-inflammation and reverse disease in a mouse model of multiple sclerosis. Mol Ther 2018; 26(1): 173-83.
[http://dx.doi.org/10.1016/j.ymthe.2017.09.001] [PMID: 28943274]
[2]
Ascherio A, Munger KL. Epidemiology of multiple sclerosis: From risk factors to prevention—an update. Semin Neurol 2016; 36(2): 103-14.
[http://dx.doi.org/10.1055/s-0036-1579693] [PMID: 27116717]
[3]
Duquette P. The increased susceptibility of women to multiple sclerosis. Mult Scler J 1998; 4(6): 511-2.
[http://dx.doi.org/10.1177/135245859800400612]
[4]
Edo Á, Espinosa-Parrilla JF. Soluble interleukin 23 receptor gene therapy with adeno-associated vectors for the treatment of multiple sclerosis. Neural Regen Res 2017; 12(10): 1605-6.
[http://dx.doi.org/10.4103/1673-5374.217327] [PMID: 29171419]
[5]
Eskandarieh S, Heydarpour P, Minagar A, Pourmand S, Sahraian MA. Multiple Sclerosis Epidemiology in East Asia, South East Asia and South Asia: A Systematic Review. Neuroepidemiology 2016; 46(3): 209-21.
[http://dx.doi.org/10.1159/000444019] [PMID: 26901651]
[6]
Hamana A, Takahashi Y, Tanioka A, Nishikawa M, Takakura Y. Safe and effective interferon-beta gene therapy for the treatment of multiple sclerosis by regulating biological activity through the design of interferon-beta-galectin-9 fusion proteins. Int J Pharm 2018; 536(1): 310-7.
[http://dx.doi.org/10.1016/j.ijpharm.2017.12.010] [PMID: 29217470]
[7]
Moghadam S, Erfanmanesh M, Esmaeilzadeh A. Interleukin 35 and Hepatocyte Growth Factor; as a novel combined immune gene therapy for Multiple Sclerosis disease. Med Hypotheses 2017; 109(1): 102-5.
[http://dx.doi.org/10.1016/j.mehy.2017.09.017] [PMID: 29150266]
[8]
Madireddy L, Patsopoulos NA, Cotsapas C, et al. Consortium IMSG.. A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nat Commun 2019; 10: 2236.
[http://dx.doi.org/10.1038/s41467-019-09773-y]
[9]
Nociti V, Santoro M, Quaranta D, et al. BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression. PLoS One 2018; 13(10): e0206140
[http://dx.doi.org/10.1371/journal.pone.0206140] [PMID: 30352103]
[10]
Boivin N, Baillargeon J, Doss PMIA, Roy A-P, Rangachari M. Interferon-β suppresses murine Th1 cell function in the absence of antigen-presenting cells. PLoS One 2015; 10(4): e0124802
[http://dx.doi.org/10.1371/journal.pone.0124802] [PMID: 25885435]
[11]
Rangachari M, Kuchroo VK. Using EAE to better understand principles of immune function and autoimmune pathology. J Autoimmun 2013; 45(1): 31-9.
[http://dx.doi.org/10.1016/j.jaut.2013.06.008] [PMID: 23849779]
[12]
Comi G. Disease-modifying treatments for progressive multiple sclerosis. Mult Scler 2013; 19(11): 1428-36.
[http://dx.doi.org/10.1177/1352458513502572] [PMID: 24062415]
[13]
Kremer D, Küry P, Dutta R. Promoting remyelination in multiple sclerosis: current drugs and future prospects. Mult Scler 2015; 21(5): 541-9.
[http://dx.doi.org/10.1177/1352458514566419] [PMID: 25623245]
[14]
Weiner LP, Louie KA, Atalla LR, et al. Gene therapy in a murine model for clinical application to multiple sclerosis. Ann Neurol 2004; 55(3): 390-9.
[http://dx.doi.org/10.1002/ana.10858] [PMID: 14991817]
[15]
Sun L, Qi X, Hauswirth W, Guy J. AAV-mediated Sod2 gene expression driven by a pro-inflammatory inducible promoter: A novel method for gene therapy of multiple sclerosis. Invest Ophthalmol Vis Sci 2003; 44(13): 628-28.
[16]
Gharibi T, Ahmadi M, Seyfizadeh N, Jadidi-Niaragh F, Yousefi M. Immunomodulatory characteristics of mesenchymal stem cells and their role in the treatment of multiple sclerosis. Cell Immunol 2015; 293(2): 113-21.
[http://dx.doi.org/10.1016/j.cellimm.2015.01.002] [PMID: 25596473]
[17]
Landi D, Albanese M, Buttari F, et al. Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study. PLoS One 2017; 12(7): e0165415
[http://dx.doi.org/10.1371/journal.pone.0165415] [PMID: 28686675]
[18]
Martino G, Furlan R, Comi G, Adorini L. The ependymal route to the CNS: an emerging gene-therapy approach for MS. Trends Immunol 2001; 22(9): 483-90.
[http://dx.doi.org/10.1016/S1471-4906(01)01990-1] [PMID: 11525938]
[19]
Muls N, Nasr Z, Dang HA, Sindic C, van Pesch V. IL-22, GM-CSF and IL-17 in peripheral CD4+ T cell subpopulations during multiple sclerosis relapses and remission. Impact of corticosteroid therapy. PLoS One 2017; 12(3): e0173780
[http://dx.doi.org/10.1371/journal.pone.0173780] [PMID: 28301515]
[20]
Guo X-L, Chung T-H, Qin Y, et al. Hemophilia gene therapy: New development from bench to bed side. Curr Gene Ther 2019; 19(4): 264-73.
[http://dx.doi.org/10.2174/1566523219666190924121836] [PMID: 31549954]
[21]
Yu B, Wu C, Li T, Qin F, Yuan J. Advances in gene therapy for erectile dysfunction: Promises and challenges. Curr Gene Ther 2018; 18(6): 351-65.
[http://dx.doi.org/10.2174/1566523218666181004145424] [PMID: 30289066]
[22]
Zhang X-P, Zhang W-T, Qiu Y, Ju M-J, Tu G-W, Luo Z. Understanding gene therapy in acute respiratory distress syndrome. Curr Gene Ther 2019; 19(2): 93-9.
[http://dx.doi.org/10.2174/1566523219666190702154817] [PMID: 31267871]
[23]
Baker D, Hankey DJ. Gene therapy in autoimmune, demyelinating disease of the central nervous system. Gene Ther 2003; 10(10): 844-53.
[http://dx.doi.org/10.1038/sj.gt.3302025] [PMID: 12732870]
[24]
Hosseini A, Estiri H, Niaki HA, et al. Multiple sclerosis gene therapy using recombinant viral vectors: Overexpression of IL-4, IL-10 and leukemia inhibitory factor in wharton’s jelly stem cells in the EAE mice model. Cell J 2017; 19(3): 361-74.
[PMID: 28836399]
[25]
Vandamme C, Adjali O, Mingozzi F. Unraveling the complex story of immune responses to AAV vectors trial after trial. Hum Gene Ther 2017; 28(11): 1061-74.
[http://dx.doi.org/10.1089/hum.2017.150] [PMID: 28835127]
[26]
Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol 2015; 15(9): 545-58.
[http://dx.doi.org/10.1038/nri3871] [PMID: 26250739]
[27]
Major EO, Yousry TA, Clifford DB. Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned. Lancet Neurol 2018; 17(5): 467-80.
[http://dx.doi.org/10.1016/S1474-4422(18)30040-1] [PMID: 29656742]
[28]
Rahmanzadeh R, Brück W, Minagar A, Sahraian MA. Multiple sclerosis pathogenesis: missing pieces of an old puzzle. Rev Neurosci 2018; 30(1): 67-83.
[http://dx.doi.org/10.1515/revneuro-2018-0002] [PMID: 29883325]
[29]
Bonin S, Zanotta N, Sartori A, et al. Cerebrospinal fluid cytokine expression profile in multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. Immunol Invest 2018; 47(2): 135-45.
[http://dx.doi.org/10.1080/08820139.2017.1405978] [PMID: 29182448]
[30]
Loveless S, Neal JW, Howell OW, et al. Tissue microarray methodology identifies complement pathway activation and dysregulation in progressive multiple sclerosis. Brain Pathol 2018; 28(4): 507-20.
[http://dx.doi.org/10.1111/bpa.12546] [PMID: 28707765]
[31]
Storch MK, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H. Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann Neurol 1998; 43(4): 465-71.
[http://dx.doi.org/10.1002/ana.410430409] [PMID: 9546327]
[32]
Nave K-A, Ehrenreich H. Time to revisit oligodendrocytes in multiple sclerosis. Nat Med 2019; 25(3): 364-6.
[http://dx.doi.org/10.1038/s41591-019-0388-4] [PMID: 30804516]
[33]
De Andres C, García MI, Goicoechea H, et al. Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers. Pharmacogenomics J 2018; 18(1): 98-105.
[http://dx.doi.org/10.1038/tpj.2016.71] [PMID: 27670768]
[34]
Konjevic Sabolek M, Held K, Beltrán E, et al. Communication of CD8+ T cells with mononuclear phagocytes in multiple sclerosis. Ann Clin Transl Neurol 2019; 6(7): 1151-64.
[http://dx.doi.org/10.1002/acn3.783] [PMID: 31353869]
[35]
Smith MD, Calabresi PA, Bhargava P. Dimethyl fumarate treatment alters NK cell function in multiple sclerosis. Eur J Immunol 2018; 48(2): 380-3.
[http://dx.doi.org/10.1002/eji.201747277] [PMID: 29108094]
[36]
Matveeva O, Bogie JFJ, Hendriks JJA, Linker RA, Haghikia A, Kleinewietfeld M. Western lifestyle and immunopathology of multiple sclerosis. Ann N Y Acad Sci 2018; 1417(1): 71-86.
[http://dx.doi.org/10.1111/nyas.13583] [PMID: 29377214]
[37]
Quintana FJ, Pérez-Sánchez S, Farez MF. [Immunopathology of multiple sclerosis]. Medicina (B Aires) 2014; 74(5): 404-10.
[PMID: 25347906]
[38]
Faissner S, Gold R. Efficacy and safety of the newer multiple sclerosis drugs approved since 2010. CNS Drugs 2018; 32(3): 269-87.
[http://dx.doi.org/10.1007/s40263-018-0488-6] [PMID: 29600441]
[39]
Alroughani R, Inshasi JS, Deleu D, et al. An overview of high-efficacy drugs for multiple sclerosis: Gulf region expert opinion. Neurol Ther 2019; 8(1): 13-23.
[http://dx.doi.org/10.1007/s40120-019-0129-0] [PMID: 30875021]
[40]
Rafiee ZA, Askari M, Azadani NN, et al. Mechanism and adverse effects of multiple sclerosis drugs: a review article. Part 1. Int J Physiol Pathophysiol Pharmacol 2019; 11(4): 95-104.
[PMID: 31523357]
[41]
Rafiee ZA, Ghadimi K, Ataei A, et al. Mechanism and adverse effects of multiple sclerosis drugs: a review article. Part 2. Int J Physiol Pathophysiol Pharmacol 2019; 11(4): 105-14.
[PMID: 31523358]
[42]
Tuosto L. Targeting inflammatory T cells in multiple sclerosis: Current therapies and future challenges. Austin J Mult Scler & Neuroimmunol 2015; 2(1): 1-9.
[http://dx.doi.org/10.26420/austinjmultsclerneuroimmunol.2015.1009]
[43]
Torkildsen Ø, Myhr KM, Bø L. Disease-modifying treatments for multiple sclerosis - a review of approved medications. Eur J Neurol 2016; 23(1)(Suppl. 1): 18-27.
[http://dx.doi.org/10.1111/ene.12883] [PMID: 26563094]
[44]
D’Amico E, Zanghì A, Leone C, Tumani H, Patti F. Treatment-related progressive multifocal leukoencephalopathy in multiple sclerosis: A comprehensive review of current evidence and future needs. Drug Saf 2016; 39(12): 1163-74.
[http://dx.doi.org/10.1007/s40264-016-0461-6] [PMID: 27696299]
[45]
Ontaneda D, Fox RJ. Progressive multiple sclerosis. Curr Opin Neurol 2015; 28(3): 237-43.
[http://dx.doi.org/10.1097/WCO.0000000000000195] [PMID: 25887766]
[46]
Stromnes IM, Goverman JM. Active induction of experimental allergic encephalomyelitis. Nat Protoc 2006; 1(4): 1810-9.
[http://dx.doi.org/10.1038/nprot.2006.285] [PMID: 17487163]
[47]
Jaini R, Hannaman D, Johnson JM, et al. Gene-based intramuscular interferon-β therapy for experimental autoimmune encephalomyelitis. Mol Ther 2006; 14(3): 416-22.
[http://dx.doi.org/10.1016/j.ymthe.2006.04.009] [PMID: 16782409]
[48]
Hamana A, Takahashi Y, Tanioka A, Nishikawa M, Takakura Y. Amelioration of experimental autoimmune encephalomyelitis in mice by interferon-beta gene therapy, using a long-term expression plasmid vector. Mol Pharm 2017; 14(4): 1212-7.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b01093] [PMID: 28257578]
[49]
Vosslamber S, van der Voort LF, van den Elskamp IJ, et al. Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis. Genes Immun 2011; 12(6): 466-72.
[http://dx.doi.org/10.1038/gene.2011.18] [PMID: 21471993]
[50]
Ryu CH, Park KY, Hou Y, Jeong CH, Kim SM, Jeun S-S. Gene therapy of multiple sclerosis using interferon β-secreting human bone marrow mesenchymal stem cells. BioMed Res Int 2013; 2013: 696738
[http://dx.doi.org/10.1155/2013/696738] [PMID: 23710456]
[51]
Zhu J, Liu J-Q, Liu Z, et al. Interleukin-27 Gene therapy prevents the development of autoimmune encephalomyelitis but fails to attenuate established inflammation due to the expansion of CD11b+Gr-1+ myeloid cells. Front Immunol 2018; 9: 873.
[http://dx.doi.org/10.3389/fimmu.2018.00873] [PMID: 29740452]
[52]
Mathisen PM, Yu M, Yin L, et al. Th2 T cells expressing transgene PDGF-A serve as vectors for gene therapy in autoimmune demyelinating disease. J Autoimmun 1999; 13(1): 31-8.
[http://dx.doi.org/10.1006/jaut.1999.0287] [PMID: 10441165]
[53]
Park I-K, Hiraki K, Kohyama K, Matsumoto Y. Differential effects of decoy chemokine (7ND) gene therapy on acute, biphasic and chronic autoimmune encephalomyelitis: implication for pathomechanisms of lesion formation. J Neuroimmunol 2008; 194(1-2): 34-43.
[http://dx.doi.org/10.1016/j.jneuroim.2007.11.012] [PMID: 18155779]
[54]
Makar TK, Bever CT, Singh IS, et al. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle. J Neuroimmunol 2009; 210(1-2): 40-51.
[http://dx.doi.org/10.1016/j.jneuroim.2009.02.017] [PMID: 19361871]
[55]
Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med 2007; 4(4): e124
[http://dx.doi.org/10.1371/journal.pmed.0040124] [PMID: 17425404]
[56]
Marin-Bañasco C, Benabdellah K, Melero-Jerez C, et al. Gene therapy with mesenchymal stem cells expressing IFN-ß ameliorates neuroinflammation in experimental models of multiple sclerosis. Br J Pharmacol 2017; 174(3): 238-53.
[http://dx.doi.org/10.1111/bph.13674] [PMID: 27882538]
[57]
Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol 2007; 4(1): 50-7.
[PMID: 17652844]
[58]
Karimfar MH, Noorozian M, Mastery Farahani R, et al. Stable transfection of pEGFP-N1-MOG plasmid to utilize in multiple sclerosis gene therapy. Anat Sci J 2015; 12(1): 3-8.
[59]
Louie KA, Weiner LP, Du J, et al. Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis. Gene Ther 2005; 12(14): 1145-53.
[http://dx.doi.org/10.1038/sj.gt.3302503] [PMID: 15772685]
[60]
Cobo M, Anderson P, Benabdellah K, et al. Mesenchymal stem cells expressing vasoactive intestinal peptide ameliorate symptoms in a model of chronic multiple sclerosis. Cell Transplant 2013; 22(5): 839-54.
[http://dx.doi.org/10.3727/096368912X657404] [PMID: 23031550]
[61]
Eixarch H, Espejo C, Gómez A, et al. Tolerance induction in experimental autoimmune encephalomyelitis using non-myeloablative hematopoietic gene therapy with autoantigen. Mol Ther 2009; 17(5): 897-905.
[http://dx.doi.org/10.1038/mt.2009.42] [PMID: 19277013]
[62]
Ruffini F, Furlan R, Poliani PL, et al. Fibroblast growth factor-II gene therapy reverts the clinical course and the pathological signs of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Ther 2001; 8(16): 1207-13.
[http://dx.doi.org/10.1038/sj.gt.3301523] [PMID: 11509953]
[63]
Sloane E, Ledeboer A, Seibert W, 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.
[http://dx.doi.org/10.1016/j.bbi.2008.09.004] [PMID: 18835435]
[64]
Butti E, Bergami A, Recchia A, et al. IL4 gene delivery to the CNS recruits regulatory T cells and induces clinical recovery in mouse models of multiple sclerosis. Gene Ther 2008; 15(7): 504-15.
[http://dx.doi.org/10.1038/gt.2008.10] [PMID: 18239607]
[65]
Butti E, Recchia A, Bergami A, et al. Clinical and functional recovery from experimental autoimmune encephalomyelitis by intracisternal delivery of il4 from a helper-dependent adenoviral vector. A pre-clinical model of gene therapy of multiple sclerosis. Mol Ther 2004; 9(1): 19-20.
[PMID: 15233938]
[66]
Furlan R, Poliani PL, Marconi PC, et al. Central nervous system gene therapy with interleukin-4 inhibits progression of ongoing relapsing-remitting autoimmune encephalomyelitis in Biozzi AB/H mice. Gene Ther 2001; 8(1): 13-9.
[http://dx.doi.org/10.1038/sj.gt.3301357] [PMID: 11402297]
[67]
Grace PM, Loram LC, Christianson JP, 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 2017; 59: 49-54.
[http://dx.doi.org/10.1016/j.bbi.2016.05.012] [PMID: 27189037]
[68]
Slaets H, Hendriks JJ, Van den Haute C, et al. CNS-targeted LIF expression improves therapeutic efficacy and limits autoimmune-mediated demyelination in a model of multiple sclerosis. Mol Ther 2010; 18(4): 684-91.
[http://dx.doi.org/10.1038/mt.2009.311] [PMID: 20068552]
[69]
Furlan R, Bergami A, Brambilla E, et al. HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG(35-55)-induced experimental autoimmune encephalomyelitis in C57BL/6 mice. Gene Ther 2007; 14(1): 93-8.
[http://dx.doi.org/10.1038/sj.gt.3302805] [PMID: 16929354]
[70]
Broberg EK, Salmi AA, Hukkanen V. IL-4 is the key regulator in herpes simplex virus-based gene therapy of BALB/c experimental autoimmune encephalomyelitis. Neurosci Lett 2004; 364(3): 173-8.
[http://dx.doi.org/10.1016/j.neulet.2004.04.059] [PMID: 15196670]
[71]
Ganea D, Toscano M, Emig F, Hooper K. Neuropeptides as cell gene therapy in experimental autoimmune encephalomyelitis. Brain Behav Immun 2013; 32: e14
[http://dx.doi.org/10.1016/j.bbi.2013.07.060]
[72]
Xu B, Scott DW. A novel retroviral gene therapy approach to inhibit specific antibody production and suppress experimental autoimmune encephalomyelitis induced by MOG and MBP. Clin Immunol 2004; 111(1): 47-52.
[http://dx.doi.org/10.1016/j.clim.2003.12.013] [PMID: 15093551]
[73]
Talla V, Koilkonda R, Guy J. Gene therapy with single-subunit yeast NADH-Ubiquinone Oxidoreductase (NDI1) improves the visual function in experimental autoimmune encephalomyelitis (EAE) mice model of Multiple Sclerosis (MS). Mol Neurobiol 2020.
[http://dx.doi.org/10.1007/s12035-019-01857-6] [PMID: 31900864]
[74]
Talla V, Porciatti V, Chiodo V, Boye SL, Hauswirth WW, Guy J. Gene therapy with mitochondrial heat shock protein 70 suppresses visual loss and optic atrophy in experimental autoimmune encephalomyelitis. Invest Ophthalmol Vis Sci 2014; 55(8): 5214-26.
[http://dx.doi.org/10.1167/iovs.14-14688] [PMID: 25015358]
[75]
Javed A, Reder AT. Therapeutic role of beta-interferons in multiple sclerosis. Pharmacol Ther 2006; 110(1): 35-56.
[http://dx.doi.org/10.1016/j.pharmthera.2005.08.011] [PMID: 16229894]
[76]
Massacesi L, Tramacere I, Amoroso S, et al. Azathioprine versus beta interferons for relapsing-remitting multiple sclerosis: a multicentre randomized non-inferiority trial. PLoS One 2014; 9(11)e113371
[http://dx.doi.org/10.1371/journal.pone.0113371] [PMID: 25402490]
[77]
Melendez-Torres GJ, Armoiry X, Court R, et al. Comparative effectiveness of beta-interferons and glatiramer acetate for relapsing-remitting multiple sclerosis: systematic review and network meta-analysis of trials including recommended dosages. BMC Neurol 2018; 18(1): 162.
[http://dx.doi.org/10.1186/s12883-018-1162-9] [PMID: 30285675]
[78]
Neuhaus O, Farina C, Wekerle H, Hohlfeld R. Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology 2001; 56(6): 702-8.
[http://dx.doi.org/10.1212/WNL.56.6.702] [PMID: 11288751]
[79]
Aharoni R, Schottlender N, Bar-Lev DD, et al. Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate. Sci Rep 2019; 9(1): 4140.
[http://dx.doi.org/10.1038/s41598-019-40713-4] [PMID: 30858445]
[80]
Chun J, Kihara Y, Jonnalagadda D, Blaho VA. Fingolimod: Lessons learned and new opportunities for treating multiple sclerosis and other disorders. Annu Rev Pharmacol Toxicol 2019; 59(1): 149-70.
[http://dx.doi.org/10.1146/annurev-pharmtox-010818-021358] [PMID: 30625282]
[81]
Cohen JA, Barkhof F, Comi G, et al. TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362(5): 402-15.
[http://dx.doi.org/10.1056/NEJMoa0907839] [PMID: 20089954]
[82]
O’Connor P, Wolinsky JS, Confavreux C, et al. TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365(14): 1293-303.
[http://dx.doi.org/10.1056/NEJMoa1014656] [PMID: 21991951]
[83]
Bar-Or A, Pachner A, Menguy-Vacheron F, Kaplan J, Wiendl H. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs 2014; 74(6): 659-74.
[http://dx.doi.org/10.1007/s40265-014-0212-x] [PMID: 24740824]
[84]
Bomprezzi R. Dimethyl fumarate in the treatment of relapsing-remitting multiple sclerosis: an overview. Ther Adv Neurol Disorder 2015; 8(1): 20-30.
[http://dx.doi.org/10.1177/1756285614564152] [PMID: 25584071]
[85]
Linker RA, Gold R. Dimethyl fumarate for treatment of multiple sclerosis: mechanism of action, effectiveness, and side effects. Curr Neurol Neurosci Rep 2013; 13(11): 394.
[http://dx.doi.org/10.1007/s11910-013-0394-8] [PMID: 24061646]
[86]
Cerles O, Gonçalves TC, Chouzenoux S, et al. Preventive action of benztropine on platinum-induced peripheral neuropathies and tumor growth. Acta Neuropathol Commun 2019; 7(1): 9.
[http://dx.doi.org/10.1186/s40478-019-0657-y] [PMID: 30657060]
[87]
Nair S, Saeed O, Shahab H, Sedky K, Garver D, Lippmann S. Sudden dysphagia with uvular enlargement following the initiation of risperidone which responded to benztropine: was this an extrapyramidal side effect? Gen Hosp Psychiatry 2001; 23(4): 231-2.
[http://dx.doi.org/10.1016/S0163-8343(01)00145-1] [PMID: 11569473]
[88]
Coles AJ, Compston DA, Selmaj KW, et al. CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med 2008; 359(17): 1786-801.
[http://dx.doi.org/10.1056/NEJMoa0802670] [PMID: 18946064]
[89]
Coles AJ, Twyman CL, Arnold DL, et al. CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380(9856): 1829-39.
[http://dx.doi.org/10.1016/S0140-6736(12)61768-1] [PMID: 23122650]
[90]
Grüter T, Metz I, Gahlen A, et al. Mitoxantrone treatment in a patient with multiple sclerosis and pattern III lesions. Clin Exp Neuroimmunol 2018; 9(3): 169-72.
[http://dx.doi.org/10.1111/cen3.12466]
[91]
Hartung H-P, Gonsette R, König N, et al. Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360(9350): 2018-25.
[http://dx.doi.org/10.1016/S0140-6736(02)12023-X] [PMID: 12504397]
[92]
Polman CH, O’Connor PW, Havrdova E, et al. AFFIRM Investigators. 4 A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354(9): 899-910.
[http://dx.doi.org/10.1056/NEJMoa044397] [PMID: 16510744]
[93]
Serafini B, Zandee S, Rosicarelli B, et al. Epstein-Barr virus-associated immune reconstitution inflammatory syndrome as possible cause of fulminant multiple sclerosis relapse after natalizumab interruption. J Neuroimmunol 2018; 319(1): 9-12.
[http://dx.doi.org/10.1016/j.jneuroim.2018.03.011] [PMID: 29685294]

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