Novel Insights and Therapeutics in Multiple Sclerosis

Overview

Journal F1000Res

Specialties Biomedical Engineering
Science

Date 2015 Sep 5

PMID 26339480

Citations 6

Authors

Catriona A Wagner

Joan M Goverman

Affiliations

Soon will be listed here.

Abstract

The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

Citing Articles

Sex-Specific Environmental Impacts on Initiation and Progression of Multiple Sclerosis.

Leffler J, Trend S, Gorman S, Hart P Front Neurol. 2022; 13:835162.

PMID: 35185777 PMC: 8850837. DOI: 10.3389/fneur.2022.835162.

Mechanisms of M2 Macrophage-Derived Exosomal Long Non-coding RNA PVT1 in Regulating Th17 Cell Response in Experimental Autoimmune Encephalomyelitisa.

Wu L, Xia J, Li D, Kang Y, Fang W, Huang P Front Immunol. 2020; 11:1934.

PMID: 33013847 PMC: 7500097. DOI: 10.3389/fimmu.2020.01934.

Monocytes and Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures in Experimental Model of Multiple Sclerosis.

Monaghan K, Zheng W, Hu G, Wan E Front Immunol. 2019; 10:2779.

PMID: 31849962 PMC: 6889845. DOI: 10.3389/fimmu.2019.02779.

OLT1177 (Dapansutrile), a Selective NLRP3 Inflammasome Inhibitor, Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis.

Sanchez-Fernandez A, Skouras D, Dinarello C, Lopez-Vales R Front Immunol. 2019; 10:2578.

PMID: 31736980 PMC: 6839275. DOI: 10.3389/fimmu.2019.02578.

Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders.

Riazifar M, Mohammadi M, Pone E, Yeri A, Lasser C, Segaliny A ACS Nano. 2019; 13(6):6670-6688.

PMID: 31117376 PMC: 6880946. DOI: 10.1021/acsnano.9b01004.

References

Ji Q, Castelli L, Goverman J . MHC class I-restricted myelin epitopes are cross-presented by Tip-DCs that promote determinant spreading to CD8⁺ T cells. Nat Immunol. 2013; 14(3):254-61. PMC: 3581685. DOI: 10.1038/ni.2513. View

Noster R, Riedel R, Mashreghi M, Radbruch H, Harms L, Haftmann C . IL-17 and GM-CSF expression are antagonistically regulated by human T helper cells. Sci Transl Med. 2014; 6(241):241ra80. DOI: 10.1126/scitranslmed.3008706. View

Frischer J, Bramow S, Dal-Bianco A, Lucchinetti C, Rauschka H, Schmidbauer M . The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009; 132(Pt 5):1175-89. PMC: 2677799. DOI: 10.1093/brain/awp070. View

Panitch H, Miller A, Paty D, Weinshenker B . Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology. 2004; 63(10):1788-95. DOI: 10.1212/01.wnl.0000146958.77317.3e. View

Coles A, Compston D, Selmaj K, Lake S, Moran S, Margolin D . Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008; 359(17):1786-801. DOI: 10.1056/NEJMoa0802670. View

Krishnamoorthy G, Lassmann H, Wekerle H, Holz A . Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest. 2006; 116(9):2385-92. PMC: 1555668. DOI: 10.1172/JCI28330. View

Brynedal B, Duvefelt K, Jonasdottir G, Roos I, Akesson E, Palmgren J . HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis. PLoS One. 2007; 2(7):e664. PMC: 1919434. DOI: 10.1371/journal.pone.0000664. View

Sawcer S, Hellenthal G, Pirinen M, Spencer C, Patsopoulos N, Moutsianas L . Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011; 476(7359):214-9. PMC: 3182531. DOI: 10.1038/nature10251. View

Jiang H, Zhang S, Pernis B . Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science. 1992; 256(5060):1213-5. DOI: 10.1126/science.256.5060.1213. View

10.

Segal B, Shevach E . IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med. 1996; 184(2):771-5. PMC: 2192714. DOI: 10.1084/jem.184.2.771. View

11.

Weber M, Prodhomme T, Patarroyo J, Molnarfi N, Karnezis T, Lehmann-Horn K . B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann Neurol. 2010; 68(3):369-83. PMC: 3375897. DOI: 10.1002/ana.22081. View

12.

Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H . Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000; 47(6):707-17. DOI: 10.1002/1531-8249(200006)47:6<707::aid-ana3>3.0.co;2-q. View

13.

Stoolman J, Duncker P, Huber A, Segal B . Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis. J Immunol. 2014; 193(2):564-70. PMC: 4091641. DOI: 10.4049/jimmunol.1400825. View

14.

Goverman J . Autoimmune T cell responses in the central nervous system. Nat Rev Immunol. 2009; 9(6):393-407. PMC: 2813731. DOI: 10.1038/nri2550. View

15.

Fischer M, Wimmer I, Hoftberger R, Gerlach S, Haider L, Zrzavy T . Disease-specific molecular events in cortical multiple sclerosis lesions. Brain. 2013; 136(Pt 6):1799-815. PMC: 3673462. DOI: 10.1093/brain/awt110. View

16.

Mars L, Saikali P, Liblau R, Arbour N . Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiple sclerosis and its animal models. Biochim Biophys Acta. 2010; 1812(2):151-61. PMC: 5052066. DOI: 10.1016/j.bbadis.2010.07.006. View

17.

Lublin F, Reingold S . Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996; 46(4):907-11. DOI: 10.1212/wnl.46.4.907. View

18.

Perchellet A, Stromnes I, Pang J, Goverman J . CD8+ T cells maintain tolerance to myelin basic protein by 'epitope theft'. Nat Immunol. 2004; 5(6):606-14. DOI: 10.1038/ni1073. View

19.

Simmons S, Liggitt D, Goverman J . Cytokine-regulated neutrophil recruitment is required for brain but not spinal cord inflammation during experimental autoimmune encephalomyelitis. J Immunol. 2014; 193(2):555-63. PMC: 4123857. DOI: 10.4049/jimmunol.1400807. View

20.

Kappos L, Radue E, OConnor P, Polman C, Hohlfeld R, Calabresi P . A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010; 362(5):387-401. DOI: 10.1056/NEJMoa0909494. View