Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?
Abstract
:1. A Brief Introduction to the Etiology and Symptoms of Multiple Sclerosis
2. Differential Diagnosis of Multiple Sclerosis
3. Anti-Inflammatory Treatments of MS
4. What Is Glatiramer Acetate?
5. The Pharmacological Modes-of-Action of GA
6. Conclusions
Acknowledgments
- Conflicts of Interest The authors declare no conflict of interest.
References
- Charcot, J. Histologie de la sclerose en plaques. Gaz. Hop 1868, 41, 554–555. [Google Scholar]
- Kachuck, N.J. Sustained release oral fampridine in the treatment of multiple sclerosis. Expert Opin. Pharmacother 2009, 10, 2025–2035. [Google Scholar]
- Compston, A.; Coles, A. Multiple sclerosis. Lancet 2008, 372, 1502–1517. [Google Scholar]
- Sadovnick, A.D.; Ebers, G.C. Epidemiology of multiple sclerosis: A critical overview. Can. J. Neurol. Sci 1993, 20, 17–29. [Google Scholar]
- Calabresi, P.A. Diagnosis and management of multiple sclerosis. Am. Family Phys 2004, 70, 1935–1944. [Google Scholar]
- Rosati, G. The prevalence of multiple sclerosis in the world: An update. Neurol. Sci.: Off. J. Ital. Neurol. Soc. Ital. Soc. Clin. Neurophysiol 2001, 22, 117–139. [Google Scholar]
- Stys, P.K.; Zamponi, G.W.; van Minnen, J.; Geurts, J.J. Will the real multiple sclerosis please stand up? Nat. Rev. Neurosci 2012, 13, 507–514. [Google Scholar]
- Compston, A. Genetic epidemiology of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 1997, 62, 553–561. [Google Scholar]
- Ota, K.; Matsui, M.; Milford, E.L.; Mackin, G.A.; Weiner, H.L.; Hafler, D.A. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 1990, 346, 183–187. [Google Scholar]
- Frohman, E.M.; Racke, M.K.; Raine, C.S. Multiple sclerosis—the plaque and its pathogenesis. N. Engl. J. Med 2006, 354, 942–955. [Google Scholar]
- Ascherio, A.; Munger, K.L. Environmental risk factors for multiple sclerosis. Part I: The role of infection. Ann. Neurol 2007, 61, 288–299. [Google Scholar]
- Ascherio, A.; Munger, K.L. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann. Neurol 2007, 61, 504–513. [Google Scholar]
- Ebers, G.C. Environmental factors and multiple sclerosis. Lancet Neurol 2008, 7, 268–277. [Google Scholar]
- Palacios, N.; Alonso, A.; Bronnum-Hansen, H.; Ascherio, A. Smoking and increased risk of multiple sclerosis: Parallel trends in the sex ratio reinforce the evidence. Ann. Epidemiol 2011, 21, 536–542. [Google Scholar]
- Mohr, D.C.; Hart, S.L.; Julian, L.; Cox, D.; Pelletier, D. Association between stressful life events and exacerbation in multiple sclerosis: A meta-analysis. BMJ 2004, 328. [Google Scholar] [CrossRef]
- Harkiolaki, M.; Holmes, S.L.; Svendsen, P.; Gregersen, J.W.; Jensen, L.T.; McMahon, R.; Friese, M.A.; van Boxel, G.; Etzensperger, R.; Tzartos, J.S.; et al. T cell-mediated autoimmune disease due to low-affinity crossreactivity to common microbial peptides. Immunity 2009, 30, 348–357. [Google Scholar]
- Levin, L.I.; Munger, K.L.; Rubertone, M.V.; Peck, C.A.; Lennette, E.T.; Spiegelman, D.; Ascherio, A. Multiple sclerosis and Epstein-Barr virus. JAMA 2003, 289, 1533–1536. [Google Scholar]
- DeLorenze, G.N.; Munger, K.L.; Lennette, E.T.; Orentreich, N.; Vogelman, J.H.; Ascherio, A. Epstein-Barr virus and multiple sclerosis: Evidence of association from a prospective study with long-term follow-up. Arch. Neurol 2006, 63, 839–844. [Google Scholar]
- Haahr, S.; Hollsberg, P. Multiple sclerosis is linked to Epstein-Barr virus infection. Rev. Med. Virol 2006, 16, 297–310. [Google Scholar]
- Christensen, T. HERVs in neuropathogenesis. J. Neuroimmune Pharmacol 2010, 5, 326–335. [Google Scholar]
- Sharma, P.; Azebi, S.; England, P.; Christensen, T.; Moller-Larsen, A.; Petersen, T.; Batsche, E.; Muchardt, C. Citrullination of Histone H3 Interferes with HP1-Mediated Transcriptional Repression. PLoS Genet 2012, 8, e1002934. [Google Scholar]
- Harauz, G.; Ishiyama, N.; Hill, C.M.; Bates, I.R.; Libich, D.S.; Fares, C. Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis. Micron 2004, 35, 503–542. [Google Scholar]
- Harauz, G.; Musse, A.A. A tale of two citrullines—structural and functional aspects of myelin basic protein deimination in health and disease. Neurochem. Res 2007, 32, 137–158. [Google Scholar]
- Musse, A.A.; Harauz, G. Molecular “negativity” may underlie multiple sclerosis: Role of the myelin basic protein family in the pathogenesis of MS. Int. Rev. Neurobiol 2007, 79, 149–172. [Google Scholar]
- Carrillo-Vico, A.; Leech, M.D.; Anderton, S.M. Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system. J. Immunol 2010, 184, 2839–2846. [Google Scholar]
- Sawcer, S.; Hellenthal, G.; Pirinen, M.; Spencer, C.C.; Patsopoulos, N.A.; Moutsianas, L.; Dilthey, A.; Su, Z.; Freeman, C.; Hunt, S.E.; et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011, 476, 214–219. [Google Scholar] [Green Version]
- Jersild, C.; Svejgaard, A.; Fog, T. HL-A antigens and multiple sclerosis. Lancet 1972, 1, 1240–1241. [Google Scholar]
- Naito, S.; Namerow, N.; Mickey, M.R.; Terasaki, P.I. Multiple sclerosis: Association with HL-A3. Tissue Antigen 1972, 2, 1–4. [Google Scholar]
- Ramagopalan, S.V.; Maugeri, N.J.; Handunnetthi, L.; Lincoln, M.R.; Orton, S.M.; Dyment, D.A.; Deluca, G.C.; Herrera, B.M.; Chao, M.J.; Sadovnick, A.D.; et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 2009, 5, e1000369. [Google Scholar]
- Friese, M.A.; Jakobsen, K.B.; Friis, L.; Etzensperger, R.; Craner, M.J.; McMahon, R.M.; Jensen, L.T.; Huygelen, V.; Jones, E.Y.; Bell, J.I.; et al. Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat. Med 2008, 14, 1227–1235. [Google Scholar]
- Madsen, L.S.; Andersson, E.C.; Jansson, L.; krogsgaard, M.; Andersen, C.B.; Engberg, J.; Strominger, J.L.; Svejgaard, A.; Hjorth, J.P.; Holmdahl, R.; et al. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat. Genet 1999, 23, 343–347. [Google Scholar]
- Lublin, F.D.; Reingold, S.C. 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, 907–911. [Google Scholar]
- Miller, D.; Barkhof, F.; Montalban, X.; Thompson, A.; Filippi, M. Clinically isolated syndromes suggestive of multiple sclerosis, part 2: Non-conventional MRI, recovery processes, and management. Lancet Neurol 2005, 4, 341–348. [Google Scholar]
- Miller, D.H. Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis. NeuroRx 2004, 1, 284–294. [Google Scholar]
- Flachenecker, P.; Hartung, H.P. Course of illness and prognosis of multiple sclerosis. 1: The natural illness course. Nervenarzt 1996, 67, 435–443. [Google Scholar]
- Moura, A.L.; Teixeira, R.A.; Oiwa, N.N.; Costa, M.F.; Feitosa-Santana, C.; Callegaro, D.; Hamer, R.D.; Ventura, D.F. Chromatic discrimination losses in multiple sclerosis patients with and without optic neuritis using the Cambridge Colour Test. Vis. Neurosci 2008, 25, 463–468. [Google Scholar]
- Patterson, V.H.; Heron, J.R. Visual field abnormalities in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 1980, 43, 205–209. [Google Scholar]
- Leray, E.; Yaouanq, J.; le Page, E.; Coustans, M.; Laplaud, D.; Oger, J.; Edan, G. Evidence for a two-stage disability progression in multiple sclerosis. Brain 2010, 133, 1900–1913. [Google Scholar]
- Bronnum-Hansen, H.; Koch-Henriksen, N.; Stenager, E. Trends in survival and cause of death in Danish patients with multiple sclerosis. Brain 2004, 127, 844–850. [Google Scholar]
- Weinshenker, B.G. Natural history of multiple sclerosis. Ann. Neurol 1994, 36, S6–S11. [Google Scholar]
- Beiske, A.G.; Pedersen, E.D.; Czujko, B.; Myhr, K.M. Pain and sensory complaints in multiple sclerosis. Eur. J. Neurol 2004, 11, 479–482. [Google Scholar]
- Feinstein, A. Multiple sclerosis and depression. Mult. Scler 2011, 17, 1276–1281. [Google Scholar]
- Andersson, M.; Alvarez-Cermeno, J.; Bernardi, G.; Cogato, I.; Fredman, P.; Frederiksen, J.; Fredrikson, S.; Gallo, P.; Grimaldi, L.M.; Gronning, M.; et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report. J. Neurol. Neurosurg. Psychiatry 1994, 57, 897–902. [Google Scholar]
- Polman, C.H.; Reingold, S.C.; Edan, G.; Filippi, M.; Hartung, H.P.; Kappos, L.; Lublin, F.D.; Metz, L.M.; McFarland, H.F.; O’Connor, P.W.; et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann. Neurol 2005, 58, 840–846. [Google Scholar]
- McDonald, W.I.; Compston, A.; Edan, G.; Goodkin, D.; Hartung, H.P.; Lublin, F.D.; McFarland, H.F.; Paty, D.W.; Polman, C.H.; Reingold, S.C.; et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol 2001, 50, 121–127. [Google Scholar]
- Whiting, P.; Harbord, R.; Main, C.; Deeks, J.J.; Filippini, G.; Egger, M.; Sterne, J.A. Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review. BMJ 2006, 332, 875–884. [Google Scholar]
- Miller, D.M.; Weinstock-Guttman, B.; Bethoux, F.; Lee, J.C.; Beck, G.; Block, V.; Durelli, L.; LaMantia, L.; Barnes, D.; Sellebjerg, F.; et al. A meta-analysis of methylprednisolone in recovery from multiple sclerosis exacerbations. Mult. Scler 2000, 6, 267–273. [Google Scholar]
- Martinelli Boneschi, F.; Rovaris, M.; Capra, R.; Comi, G. Mitoxantrone for multiple sclerosis. Cochrane Database Syst. Rev. 2005. [Google Scholar] [CrossRef]
- Swinburn, W.R.; Liversedge, L.A. Long-term treatment of multiple sclerosis with azathioprine. J. Neurol. Neurosurg. Psychiatry 1973, 36, 124–126. [Google Scholar]
- Casetta, I.; Iuliano, G.; Filippini, G. Azathioprine for multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2009, 80, 131–132. [Google Scholar]
- Lugaresi, A.; Caporale, C.; Farina, D.; Marzoli, F.; Bonanni, L.; Muraro, P.A.; de Luca, G.; Iarlori, C.; Gambi, D. Low-dose oral methotrexate treatment in chronic progressive multiple sclerosis. Neurol. Sci 2001, 22, 209–210. [Google Scholar]
- Goodkin, D.E.; Rudick, R.A.; VanderBrug Medendorp, S.; Greene, T.; Schwetz, K.M.; Fischer, J.; Daughtry, M.M.; Ross, J.; Van Dyke, C. Low-dose (7.5 mg) oral methotrexate for chronic progressive multiple sclerosis. Design of a randomized, placebo-controlled trial with sample size benefits from a composite outcome variable including preliminary data on toxicity. Online J. Curr. Clin. Trials 1992, 19. [Google Scholar] [PubMed]
- Weitz-Schmidt, G.; Welzenbach, K.; Brinkmann, V.; Kamata, T.; Kallen, J.; Bruns, C.; Cottens, S.; Takada, Y.; Hommel, U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med 2001, 7, 687–692. [Google Scholar]
- Kallen, J.; Welzenbach, K.; Ramage, P.; Geyl, D.; Kriwacki, R.; Legge, G.; Cottens, S.; Weitz-Schmidt, G.; Hommel, U. Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J. Mol. Biol 1999, 292, 1–9. [Google Scholar]
- Katznelson, S.; Kobashigawa, J.A. Dual roles of HMG-CoA reductase inhibitors in solid organ transplantation: lipid lowering and immunosuppression. Kidney Int. Suppl 1995, 52, S112–S115. [Google Scholar]
- Wang, J.; Xiao, Y.; Luo, M.; Luo, H. Statins for multiple sclerosis. Cochrane Database Syst. Rev. 2011, 12, CD008386. [Google Scholar]
- Cortese, I.; Chaudhry, V.; So, Y.T.; Cantor, F.; Cornblath, D.R.; Rae-Grant, A. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011, 76, 294–300. [Google Scholar]
- Achiron, A.; Kishner, I.; Sarova-Pinhas, I.; Raz, H.; Faibel, M.; Stern, Y.; Lavie, M.; Gurevich, M.; Dolev, M.; Magalashvili, D.; et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Arch. Neurol 2004, 61, 1515–1520. [Google Scholar]
- Bohn, A.B.; Nederby, L.; Harbo, T.; Skovbo, A.; Vorup-Jensen, T.; Krog, J.; Jakobsen, J.; Hokland, M.E. The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy. Eur. J. Neurol 2011, 18, 919–924. [Google Scholar]
- Kappos, L. European Study Group on interferon beta-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998, 352, 1491–1497. [Google Scholar]
- Jacobs, L.D.; Beck, R.W.; Simon, J.H.; Kinkel, R.P.; Brownscheidle, C.M.; Murray, T.J.; Simonian, N.A.; Slasor, P.J.; Sandrock, A.W. CHAMPS Study Group. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N. Engl. J. Med. 2000, 343, 898–904. [Google Scholar]
- Comi, G.; Filippi, M.; Barkhof, F.; Durelli, L.; Edan, G.; Fernandez, O.; Hartung, H.; Seeldrayers, P.; Sorensen, P.S.; Rovaris, M.; et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: A randomised study. Lancet 2001, 357, 1576–1582. [Google Scholar]
- Yednock, T.A.; Cannon, C.; Fritz, L.C.; 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. [Google Scholar]
- Steinman, L.; Zamvil, S.S. Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol 2005, 26, 565–571. [Google Scholar]
- Polman, C.H.; O’Connor, P.W.; Havrdova, E.; Hutchinson, M.; Kappos, L.; Miller, D.H.; Phillips, J.T.; Lublin, F.D.; Giovannoni, G.; Wajgt, A.; et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med 2006, 354, 899–910. [Google Scholar]
- Miller, D.H.; Soon, D.; Fernando, K.T.; MacManus, D.G.; Barker, G.J.; Yousry, T.A.; Fisher, E.; O’Connor, P.W.; Phillips, J.T.; Polman, C.H.; et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology 2007, 68, 1390–1401. [Google Scholar]
- Sorensen, P.S.; Ross, C.; Clemmesen, K.M.; Bendtzen, K.; Frederiksen, J.L.; Jensen, K.; Kristensen, O.; Petersen, T.; Rasmussen, S.; Ravnborg, M.; et al. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis. Lancet 2003, 362, 1184–1191. [Google Scholar]
- Calabresi, P.A.; Giovannoni, G.; Confavreux, C.; Galetta, S.L.; Havrdova, E.; Hutchinson, M.; Kappos, L.; Miller, D.H.; O’Connor, P.W.; Phillips, J.T.; et al. The incidence and significance of anti-natalizumab antibodies: Results from AFFIRM and SENTINEL. Neurology 2007, 69, 1391–1403. [Google Scholar]
- Bloomgren, G.; Richman, S.; Hotermans, C.; Subramanyam, M.; Goelz, S.; Natarajan, A.; Lee, S.; Plavina, T.; Scanlon, J.V.; Sandrock, A.; et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N. Engl. J. Med 2012, 366, 1870–1880. [Google Scholar]
- Tavazzi, E.; Ferrante, P.; Khalili, K. Progressive multifocal leukoencephalopathy: An unexpected complication of modern therapeutic monoclonal antibody therapies. Clin. Microbiol. Infect 2011, 17, 1776–1780. [Google Scholar]
- Vorup-Jensen, T. On the roles of polyvalent binding in immune recognition: Perspectives in the nanoscience of immunology and the immune response to nanomedicines. Adv. Drug Deliv. Rev. 2012, in press. [Google Scholar]
- Krumbholz, M.; Derfuss, T.; Hohlfeld, R.; Meinl, E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat. Rev. Neurol. 2012. [Google Scholar] [CrossRef]
- Bornstein, M.B.; Miller, A.; Slagle, S.; Weitzman, M.; Crystal, H.; Drexler, E.; Keilson, M.; Merriam, A.; Wassertheil-Smoller, S.; Spada, V.; et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N. Engl. J. Med 1987, 317, 408–414. [Google Scholar]
- Miller, A.; Spada, V.; Beerkircher, D.; Kreitman, R.R. Long-term (up to 22 years), open-label, compassionate-use study of glatiramer acetate in relapsing-remitting multiple sclerosis. Mult. Scler 2008, 14, 494–499. [Google Scholar]
- Ford, C.; Goodman, A.D.; Johnson, K.; Kachuck, N.; Lindsey, J.W.; Lisak, R.; Luzzio, C.; Myers, L.; Panitch, H.; Preiningerova, J.; et al. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: Results from the 15-year analysis of the US prospective open-label study of glatiramer acetate. Mult. Scler 2010, 16, 342–350. [Google Scholar]
- Ford, C.C.; Johnson, K.P.; Lisak, R.P.; Panitch, H.S.; Shifronis, G.; Wolinsky, J.S. A prospective open-label study of glatiramer acetate: Over a decade of continuous use in multiple sclerosis patients. Mult. Scler 2006, 12, 309–320. [Google Scholar]
- Comi, G.; Filippi, M.; Wolinsky, J.S. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging—measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann. Neurol 2001, 49, 290–297. [Google Scholar]
- Johnson, K.P.; Brooks, B.R.; Cohen, J.A.; Ford, C.C.; Goldstein, J.; Lisak, R.P.; Myers, L.W.; Panitch, H.S.; Rose, J.W.; Schiffer, R.B. The Copolymer 1 Multiple Sclerosis Study Group. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 1995, 45, 1268–1276. [Google Scholar]
- Martinelli Boneschi, F.; Rovaris, M.; Johnson, K.P.; Miller, A.; Wolinsky, J.S.; Ladkani, D.; Shifroni, G.; Comi, G.; Filippi, M. Effects of glatiramer acetate on relapse rate and accumulated disability in multiple sclerosis: Meta-analysis of three double-blind, randomized, placebo-controlled clinical trials. Mult. Scler 2003, 9, 349–355. [Google Scholar]
- La Mantia, L.; Munari, L.M.; Lovati, R. Glatiramer acetate for multiple sclerosis. Cochrane Database Syst. Rev. 2010. [Google Scholar] [CrossRef]
- Korczyn, A.D.; Nisipeanu, P. Safety profile of copolymer 1: Analysis of cumulative experience in the United States and Israel. J. Neurol 1996, 243, S23–S26. [Google Scholar]
- Copaxone 20mg/mL, Solution For Injection, Pre-Filled Syringe. Available online: http://www.medicines.org.uk/emc/medicine/17516/SPC accessed on 5 November 2012.
- Johnson, K.P.; Brooks, B.R.; Ford, C.C.; Goodman, A.; Guarnaccia, J.; Lisak, R.P.; Myers, L.W.; Panitch, H.S.; Pruitt, A.; Rose, J.W.; et al. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult. Scler 2000, 6, 255–266. [Google Scholar]
- Sellebjerg, F.; Hedegaard, C.J.; Krakauer, M.; Hesse, D.; Lund, H.; Nielsen, C.H.; Sondergaard, H.B.; Sorensen, P.S. Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis. Mult. Scler 2012, 18, 305–313. [Google Scholar]
- Sela, M. Poly(α-amino acids)—From a better understanding of immune phenomena to a drug against multiple sclerosis. Acta Polym 1998, 49, 523–525. [Google Scholar]
- Arnon, R.; Sela, M. Immunomodulation by the copolymer glatiramer acetate. J. Mol. Recognit 2003, 16, 412–421. [Google Scholar]
- Arnon, R.; Sela, M. The chemistry of the Copaxone drug. Chem. Isr 1999, 1, 12–17. [Google Scholar]
- Katchalski-Katzir, E. My contributions to science and society. J. Biol. Chem 2005, 280, 16529–16541. [Google Scholar]
- Eisenbach, M. Ephraim Katchalski-Katzir (1916–2009). Trends Biochem. Sci 2009, 34, 427–428. [Google Scholar]
- Katchalski, E.; Grossfeld, I.; Frankel, M. Poly-lysine. J. Am. Chem. Soc 1947, 69, 2564. [Google Scholar]
- Katchalski, E.; Sela, M. Synthesis and chemical properties of poly-alpha-amino acids. Adv. Protein Chem 1958, 13, 243–492. [Google Scholar]
- Pauling, L.; Corey, R.B.; Branson, H.R. The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sci. USA 1951, 37, 205–211. [Google Scholar]
- Perutz, M.F. New X-ray evidence on the configuration of polypeptide chains. Nature 1951, 167, 1053–1054. [Google Scholar]
- Rich, A.; Crick, F.H. The structure of collagen. Nature 1955, 176, 915–916. [Google Scholar]
- Engel, J.; Kurtz, J.; Katchalski, E.; Berger, A. Polymers tripeptides as collagen models. II. Conformational changes of poly(l-prolyl-glycyl-l-prolyl) in solution. J. Mol. Biol 1966, 17, 255–272. [Google Scholar]
- Levin, Y.; Berger, A.; Katchalski, E. Hydrolysis and transpeptidation of lysine peptides by trypsin. Biochem. J 1956, 63, 308–316. [Google Scholar]
- Arnon, R.; Sela, M. Studies on the chemical basis of the antigenicity of proteins. 2. Antigenic specificity of polytyrosyl gelatins. Biochem. J 1960, 75, 103–109. [Google Scholar]
- Sela, M.; Arnon, R. Studies on the chemical basis of the antigenicity of proteins. 1. Antigenicity of polypeptidyl gelatins. Biochem. J 1960, 75, 91–102. [Google Scholar]
- Sela, M.; Arnon, R. Studies on the chemical basis of the antigenicity of proteins. 3. The role of rigidity in the antigenicity of polypeptidyl gelatins. Biochem. J 1960, 77, 394–399. [Google Scholar]
- Arnon, R.; Maron, E.; Sela, M.; Anfinsen, C.B. Antibodies reactive with native lysozyme elicited by a completely synthetic antigen. Proc. Natl. Acad. Sci. USA 1971, 68, 1450–1455. [Google Scholar]
- Shaw, C.M.; Alvord, E.C., Jr; Fahlberg, W.J.; Kies, M.W. Specificity of encephalitogen-induced inhibition of experimental “allergic” encephalomyelitis in the guinea pig. J. Immunol. 1962, 89, 54–61. [Google Scholar]
- Teitelbaum, D.; Meshorer, A.; Hirshfeld, T.; Arnon, R.; Sela, M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur. J. Immunol 1971, 1, 242–248. [Google Scholar]
- Teitelbaum, D.; Gan, R.; Meshorer, A.; Hirsfeld, T.; Arnon, R.; Sela, M. Therapeutic Copolymer. U.S. Patent 3,849,550, March 1971. [Google Scholar]
- Katchalski-Katzir, E. Synthesis, physicochemical and biological properties of poly-alpha-amino acids--the simplest of protein models. Acta Biochim. Polon 1996, 43, 217–226. [Google Scholar]
- Fridkis-Hareli, M.; Santambrogio, L.; Stern, J.N.; Fugger, L.; Brosnan, C.; Strominger, J.L. Novel synthetic amino acid copolymers that inhibit autoantigen-specific T cell responses and suppress experimental autoimmune encephalomyelitis. J. Clin. Invest 2002, 109, 1635–1643. [Google Scholar]
- Capila, I.; Linhardt, R.J. Heparin-protein interactions. Angew. Chem. Int. Ed. Engl 2002, 41, 391–412. [Google Scholar]
- Venkataraman, G.; Shriver, Z.; Raman, R.; Sasisekharan, R. Sequencing complex polysaccharides. Science 1999, 286, 537–542. [Google Scholar]
- Berkowitz, S.A.; Engen, J.R.; Mazzeo, J.R.; Jones, G.B. Analytical tools for characterizing biopharmaceuticals and the implications for biosimilars. Nat. Rev. Drug Discov 2012, 11, 527–540. [Google Scholar]
- Guerrini, M.; Beccati, D.; Shriver, Z.; Naggi, A.; Viswanathan, K.; Bisio, A.; Capila, I.; Lansing, J.C.; Guglieri, S.; Fraser, B.; et al. Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Nat. Biotechnol 2008, 26, 669–675. [Google Scholar]
- Kishimoto, T.K.; Viswanathan, K.; Ganguly, T.; Elankumaran, S.; Smith, S.; Pelzer, K.; Lansing, J.C.; Sriranganathan, N.; Zhao, G.; Galcheva-Gargova, Z.; et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N. Engl. J. Med 2008, 358, 2457–2467. [Google Scholar]
- Liu, H.; Zhang, Z.; Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep 2009, 26, 313–321. [Google Scholar]
- Fridkis-Hareli, M.; Stern, J.N.; Fugger, L.; Strominger, J.L. Synthetic peptides that inhibit binding of the myelin basic protein 85–99 epitope to multiple sclerosis-associated HLA-DR2 molecules and MBP-specific T-cell responses. Human Immunol 2001, 62, 753–763. [Google Scholar]
- Teitelbaum, D.; Aharoni, R.; Sela, M.; Arnon, R. Cross-reactions and specificities of monoclonal antibodies against myelin basic protein and against the synthetic copolymer 1. Proc. Natl. Acad. Sci. USA 1991, 88, 9528–9532. [Google Scholar]
- Fridkis-Hareli, M.; Strominger, J.L. Promiscuous binding of synthetic copolymer 1 to purified HLA-DR molecules. J. Immunol 1998, 160, 4386–4397. [Google Scholar]
- Fridkis-Hareli, M.; Aharoni, R.; Teitelbaum, D.; Arnon, R.; Sela, M.; Strominger, J.L. Binding of random copolymers of three amino acids to class II MHC molecules. Int. Immunol 1999, 11, 635–641. [Google Scholar]
- Teitelbaum, D.; Fridkis-Hareli, M.; Arnon, R.; Sela, M. Copolymer 1 inhibits chronic relapsing experimental allergic encephalomyelitis induced by proteolipid protein (PLP) peptides in mice and interferes with PLP-specific T cell responses. J. Neuroimmunol 1996, 64, 209–217. [Google Scholar]
- Ben-Nun, A.; Mendel, I.; Bakimer, R.; Fridkis-Hareli, M.; Teitelbaum, D.; Arnon, R.; Sela, M.; de Rosbo, N.K. The autoimmune reactivity to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is potentially pathogenic: effect of copolymer 1 on MOG-induced disease. J. Neurol 1996, 243, S14–S22. [Google Scholar]
- Ibarra, A.; Avendano, H.; Cruz, Y. Copolymer-1 (Cop-1) improves neurological recovery after middle cerebral artery occlusion in rats. Neurosci. Lett 2007, 425, 110–113. [Google Scholar]
- Aharoni, R.; Teitelbaum, D.; Arnon, R.; Sela, M. Copolymer 1 inhibits manifestations of graft rejection. Transplantation 2001, 72, 598–605. [Google Scholar]
- Duda, P.W.; Schmied, M.C.; Cook, S.L.; Krieger, J.I.; Hafler, D.A. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J. Clin. Invest 2000, 105, 967–976. [Google Scholar]
- Berthelot, L.; Miqueu, P.; Pettre, S.; Guillet, M.; Moynard, J.; Wiertlewski, S.; Lefrere, F.; Brouard, S.; Soulillou, J.P.; Laplaud, D.A. Failure of glatiramer acetate to modify the peripheral T cell repertoire of relapsing-remitting multiple sclerosis patients. Clin. Immunol 2010, 135, 33–42. [Google Scholar]
- Aharoni, R.; Teitelbaum, D.; Sela, M.; Arnon, R. Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 1997, 94, 10821–10826. [Google Scholar]
- Kala, M.; Rhodes, S.N.; Piao, W.H.; Shi, F.D.; Campagnolo, D.I.; Vollmer, T.L. B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis. Exp. Neurol 2010, 221, 136–145. [Google Scholar]
- Racke, M.K.; Lovett-Racke, A.E. Glatiramer acetate treatment of multiple sclerosis: an immunological perspective. J. Immunol 2011, 186, 1887–1890. [Google Scholar]
- Neuhaus, O.; Farina, C.; Yassouridis, A.; Wiendl, H.; Then Bergh, F.; Dose, T.; Wekerle, H.; Hohlfeld, R. Multiple sclerosis: Comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells. Proc. Natl. Acad. Sci. USA 2000, 97, 7452–7457. [Google Scholar]
- Krogsgaard, M.; Wucherpfennig, K.W.; Cannella, B.; Hansen, B.E.; Svejgaard, A.; Pyrdol, J.; Ditzel, H.; Raine, C.; Engberg, J.; Fugger, L. Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85–99 complex. J. Exp. Med 2000, 191, 1395–1412. [Google Scholar]
- Aharoni, R.; Teitelbaum, D.; Sela, M.; Arnon, R. Bystander suppression of experimental autoimmune encephalomyelitis by T cell lines and clones of the Th2 type induced by copolymer 1. J. Neuroimmunol 1998, 91, 135–146. [Google Scholar]
- Jee, Y.; Liu, R.; Bai, X.F.; Campagnolo, D.I.; Shi, F.D.; Vollmer, T.L. Do Th2 cells mediate the effects of glatiramer acetate in experimental autoimmune encephalomyelitis? Int. Immunol 2006, 18, 537–544. [Google Scholar]
- Kipnis, J.; Yoles, E.; Porat, Z.; Cohen, A.; Mor, F.; Sela, M.; Cohen, I.R.; Schwartz, M. T cell immunity to copolymer 1 confers neuroprotection on the damaged optic nerve: possible therapy for optic neuropathies. Proc. Natl. Acad. Sci. USA 2000, 97, 7446–7451. [Google Scholar]
- Stapulionis, R.; Oliveira, C.L.P.; Gjelstrup, M.C.; Pedersen, J.S.; Hokland, M.E.; Hoffmann, S.V.; Poulsen, K.; Jacobsen, C.; Vorup-Jensen, T. Structural insight into the function of myelin basic protein as a ligand for integrin alpha(M)beta(2). J. Immunol 2008, 180, 3946–3956. [Google Scholar]
- Rathinam, V.A.; Vanaja, S.K.; Fitzgerald, K.A. Regulation of inflammasome signaling. Nat. Immunol. 2012, 13. [Google Scholar] [CrossRef]
- Gordon, S. Pattern recognition receptors: doubling up for the innate immune response. Cell 2002, 111, 927–930. [Google Scholar]
- Hynes, R.O. Integrins: bidirectional, allosteric signaling machines. Cell 2002, 110, 673–687. [Google Scholar]
- Springer, T.A. Adhesion receptors of the immune system. Nature 1990, 346, 425–434. [Google Scholar]
- Luo, B.H.; Carman, C.V.; Springer, T.A. Structural basis of integrin regulation and signaling. Annu. Rev. Immunol 2007, 25, 619–647. [Google Scholar]
- Gomez, I.G.; Tang, J.; Wilson, C.L.; Yan, W.; Heinecke, J.W.; Harlan, J.M.; Raines, E.W. Metalloproteinase-mediated Shedding of Integrin beta2 promotes macrophage efflux from inflammatory sites. J. Biol. Chem 2012, 287, 4581–4589. [Google Scholar]
- Gjelstrup, L.C.; Boesen, T.; Kragstrup, T.W.; Jorgensen, A.; Klein, N.J.; Thiel, S.; Deleuran, B.W.; Vorup-Jensen, T. Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure. J. Immunol 2010, 185, 4154–4168. [Google Scholar]
- Vorup-Jensen, T.; Carman, C.V.; Shimaoka, M.; Schuck, P.; Svitel, J.; Springer, T.A. Exposure of acidic residues as a danger signal for recognition of fibrinogen and other macromolecules by integrin alphaXbeta2. Proc. Natl. Acad. Sci. USA 2005, 102, 1614–1619. [Google Scholar]
- Vorup-Jensen, T.; Chi, L.; Gjelstrup, L.C.; Jensen, U.B.; Jewett, C.A.; Xie, C.; Shimaoka, M.; Linhardt, R.J.; Springer, T.A. Binding between the integrin alphaXbeta2 (CD11c/CD18) and heparin. J. Biol. Chem 2007, 282, 30869–30877. [Google Scholar]
- Davis, G.E. The Mac-1 and p150,95 beta 2 integrins bind denatured proteins to mediate leukocyte cell-substrate adhesion. Exp. Cell. Res 1992, 200, 242–252. [Google Scholar]
- Whitaker, J.N. Myelin basic protein in cerebrospinal fluid and other body fluids. Mult. Scler 1998, 4, 16–21. [Google Scholar]
- Constantinescu, R.; Zetterberg, H.; Holmberg, B.; Rosengren, L. Levels of brain related proteins in cerebrospinal fluid: an aid in the differential diagnosis of parkinsonian disorders. Parkinsonism Relat. Disord 2009, 15, 205–212. [Google Scholar]
- Prineas, J.W.; Graham, J.S. Multiple sclerosis: Capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann. Neurol 1981, 10, 149–158. [Google Scholar]
- Epstein, L.G.; Prineas, J.W.; Raine, C.S. Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis. J. Neurol. Sci 1983, 61, 341–348. [Google Scholar]
- Nielsen, H.H.; Ladeby, R.; Fenger, C.; Toft-Hansen, H.; Babcock, A.A.; Owens, T.; Finsen, B. Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system. J. Neuropathol. Exp. Neurol 2009, 68, 845–856. [Google Scholar]
- Ransohoff, R.M.; Kivisakk, P.; Kidd, G. Three or more routes for leukocyte migration into the central nervous system. Nat. Rev. Immunol 2003, 3, 569–581. [Google Scholar]
- Lobel, E.; Riven-Kreitman, R.; Amselem, A.; Pinchasi, I. Copolymer 1. Drug Fut 1996, 21, 131–134. [Google Scholar]
- Ziemssen, T.; Neuhaus, O.; Hohlfeld, R. Risk-benefit assessment of glatiramer acetate in multiple sclerosis. Drug Saf 2001, 24, 979–990. [Google Scholar]
- Weber, M.S.; Prod’homme, T.; Youssef, S.; Dunn, S.E.; Rundle, C.D.; Lee, L.; Patarroyo, J.C.; Stuve, O.; Sobel, R.A.; Steinman, L.; et al. Type II monocytes modulate T cell-mediated central nervous system autoimmune disease. Nat. Med 2007, 13, 935–943. [Google Scholar]
- Weber, M.S.; Starck, M.; Wagenpfeil, S.; Meinl, E.; Hohlfeld, R.; Farina, C. Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain 2004, 127, 1370–1378. [Google Scholar]
- Clausen, J.; Matzke, J.; Gerhardt, W. Agar-Gel Micro-Electrophoresis of Proteins in the Cerebrospinal Fluid Normal and Pathological Findings. Acta Neurol. Scand. Suppl 1964, 40, 49–56. [Google Scholar]
- Borlongan, C.V.; Glover, L.E.; Sanberg, P.R.; Hess, D.C. Permeating the blood brain barrier and abrogating the inflammation in stroke: Implications for stroke therapy. Curr. Pharm. Des 2012, 18, 3670–3676. [Google Scholar]
- Toker, A.; Slaney, C.Y.; Backstrom, B.T.; Harper, J.L. Glatiramer acetate treatment directly targets CD11b(+)Ly6G(-) monocytes and enhances the suppression of autoreactive T cells in experimental autoimmune encephalomyelitis. Scand. J. Immunol 2011, 74, 235–243. [Google Scholar]
- Lamers, K.J.; Vos, P.; Verbeek, M.M.; Rosmalen, F.; van Geel, W.J.; van Engelen, B.G. Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients. Brain Res. Bull 2003, 61, 261–264. [Google Scholar]
- Aharoni, R.; Kayhan, B.; Eilam, R.; Sela, M.; Arnon, R. Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ. Proc. Natl. Acad. Sci. USA 2003, 100, 14157–14162. [Google Scholar]
- Ure, D.R.; Rodriguez, M. Polyreactive antibodies to glatiramer acetate promote myelin repair in murine model of demyelinating disease. FASEB J 2002, 16, 1260–1262. [Google Scholar]
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Jalilian, B.; Einarsson, H.B.; Vorup-Jensen, T. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System? Int. J. Mol. Sci. 2012, 13, 14579-14605. https://doi.org/10.3390/ijms131114579
Jalilian B, Einarsson HB, Vorup-Jensen T. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System? International Journal of Molecular Sciences. 2012; 13(11):14579-14605. https://doi.org/10.3390/ijms131114579
Chicago/Turabian StyleJalilian, Babak, Halldór Bjarki Einarsson, and Thomas Vorup-Jensen. 2012. "Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?" International Journal of Molecular Sciences 13, no. 11: 14579-14605. https://doi.org/10.3390/ijms131114579