Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Fatty Acids and Antioxidants in Multiple Sclerosis: Therapeutic Role of GEMSP

Author(s): Pablo Ahumada-Pascual, Daniel G. Gañán, Yasmina E.B. Montero and Ana Velasco*

Volume 25 , Issue 4 , 2019

Page: [376 - 380] Pages: 5

DOI: 10.2174/1381612825666190312105755

Price: $65


Multiple sclerosis is a high-frequency neurological disorder in young adults. Although there are some genetic and environmental factors that have been related to the onset of the disease, these are still not completely understood and nowadays multiple sclerosis can neither be prevented, nor its symptom effectively treated due to disease heterogeneity. For this reason, the search of prognostic factors and new therapeutic compounds for MS has long aroused among clinicians and researchers. Among these therapeutic compounds, GEMSP, which consists of a mixture of functional constituents as fatty acids, antioxidants, free radical scavengers and amino acids linked individually to poly-L-Lysine (PL), is emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP have demonstrated that this drug strongly inhibits brain leukocyte infiltration and completely abolishes experimental autoimmune encephalomyelitis. In addition, in an open clinical trial in humans treated with GEMSP, in 72% of the cases, a positive evolution of the state of the MS patients treated with GMSP was observed. In this review a biochemical characterization of main constituents of GEMSP, which include fatty acids as oleic acid, linoleic acid or azelaic acid and the antioxidants alpha-tocopherol or ascorbic acid, will be provided in order to understand their proved therapeutic effects in MS.

Keywords: Multiple sclerosis, GEMSP, fatty acids and antioxidants, neurological disorder, fatty acid.

Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996; 46(4): 907-11.
Antel J, Antel S, Caramanos Z, Arnold DL, Kuhlmann T. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol 2012; 123(5): 627-38.
Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83(3): 278-86.
Fernández O, Agüera E, Izquierdo G, et al. Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain. PLoS One 2012; 7(5): e35600.
McQueen RB, Livingston T, Vollmer T, et al. Increased relapse activity for multiple sclerosis natalizumab users who become nonpersistent: A retrospective study. J Manag Care Spec Pharm 2015; 21(3): 210-8b.
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med 2017; 376(3): 209-20.
Hoepner R, Faissner S, Salmen A, Gold R, Chan A. Efficacy and side effects of natalizumab therapy in patients with multiple sclerosis. J Cent Nerv Syst Dis 2014; 6: 41-9.
Ferenczy MW, Marshall LJ, Nelson CD, et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 2012; 25(3): 471-506.
Brinkmann V. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol 2009; 158(5): 1173-82.
Mandal P, Gupta A, Fusi-Rubiano W, Keane PA, Yang Y. Fingolimod: Therapeutic mechanisms and ocular adverse effects. Eye 2017; 31(2): 232-40.
Cohen JA, Coles AJ, Arnold DL, 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.
Coles AJ, Twyman CL, Arnold DL, 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.
Muraro PA, Scolding NJ, Fox RJ. Rare side effects of alemtuzumab remind us of the need for postmarketing surveillance. Neurology 2018; 90(18): 819-20.
Sedal L, Winkel A, Laing J, Law LY, McDonald E. Current concepts in multiple sclerosis therapy. Degener Neurol Neuromuscul Dis 2017; 7: 109-25.
Mangas A, Coveñas R, Bodet D, de León M, Duleu S, Geffard M. Evaluation of the effects of a new drug candidate (GEMSP) in a chronic EAE model. Int J Biol Sci 2008; 4(3): 150-60.
Geffard M, Mangas A, Coveñas R. Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP). Biomed Rep 2017; 6(3): 307-13.
Mangas A, Coveñas R, Bodet D, Duleu S, Geffard M. A new drug candidate (GEMSP) for multiple sclerosis. Curr Med Chem 2009; 16(25): 3203-14.
Esparza ML, Sasaki S, Kesteloot H. Nutrition, latitude, and multiple sclerosis mortality: An ecologic study. Am J Epidemiol 1995; 142(7): 733-7.
Ghadirian P, Jain M, Ducic S, Shatenstein B, Morisset R. Nutritional factors in the aetiology of multiple sclerosis: A case-control study in Montreal, Canada. Int J Epidemiol 1998; 27(5): 845-52.
Conde C, Escribano BM, Luque E, et al. The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat. Nutr Neurosci 2018; 1-12.
Trépanier MO, Hildebrand KD, Nyamoya SD, Amor S, Bazinet RP, Kipp M. Phosphatidylcholine 36:1 concentration decreases along with demyelination in the cuprizone animal model and in post-mortem multiple sclerosis brain tissue. J Neurochem 2018; 145(6): 504-15.
Tabernero A, Lavado EM, Granda B, Velasco A, Medina JM. Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes. J Neurochem 2001; 79(3): 606-16.
Medina JM, Tabernero A. Astrocyte-synthesized oleic acid behaves as a neurotrophic factor for neurons. J Physiol Paris 2002; 96(3-4): 265-71.
Tabernero A, Velasco A, Granda B, Lavado EM, Medina JM. Transcytosis of albumin in astrocytes activates the sterol regulatory element-binding protein-1, which promotes the synthesis of the neurotrophic factor oleic acid. J Biol Chem 2002; 277(6): 4240-6.
Song SY, Kato C, Adachi E, et al. Expression of an acyl-CoA synthetase, lipidosin, in astrocytes of the murine brain and its up-regulation during remyelination following cuprizone-induced demyelination. J Neurosci Res 2007; 85(16): 3586-97.
Garbay B, Boiron-Sargueil F, Shy M, et al. Regulation of oleoyl-CoA synthesis in the peripheral nervous system: Demonstration of a link with myelin synthesis. J Neurochem 1998; 71(4): 1719-26.
Edmond J, Higa TA, Korsak RA, Bergner EA, Lee WN. Fatty acid transport and utilization for the developing brain. J Neurochem 1998; 70(3): 1227-34.
Chen CT, Green JT, Orr SK, Bazinet RP. Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot Essent Fatty Acids 2008; 79(3-5): 85-91.
von Geldern G, Mowry EM. The influence of nutritional factors on the prognosis of multiple sclerosis. Nat Rev Neurol 2012; 8(12): 678-89.
Mehta LR, Dworkin RH, Schwid SR. Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis. Nat Clin Pract Neurol 2009; 5(2): 82-92.
Stachowska E, Dolegowska B, Dziedziejko V, et al. Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages. J Physiol Pharmacol 2009; 60(1): 77-85.
Callegari PE, Zurier RB. Botanical lipids: potential role in modulation of immunologic responses and inflammatory reactions. Rheum Dis Clin North Am 1991; 17(2): 415-25.
Gil A. Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother 2002; 56(8): 388-96.
Namazi MR. The beneficial and detrimental effects of linoleic acid on autoimmune disorders. Autoimmunity 2004; 37(1): 73-5.
Mertin J, Stackpoole A, Shumway SJ. Prostaglandins and cell-mediated immunity. The role of prostaglandin E1 in the induction of host-versus-graft and graft-versus-host reactions in mice. Transplantation 1984; 37(4): 396-402.
Mertin J, Stackpoole A, Shumway S. Nutrition and immunity: the immunoregulatory effect of n-6 essential fatty acids is mediated through prostaglandin E. Int Arch Allergy Appl Immunol 1985; 77(4): 390-5.
Santoli D, Zurier RB. Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism. J Immunol 1989; 143(4): 1303-9.
Rossetti RG, Seiler CM, DeLuca P, Laposata M, Zurier RB. Oral administration of unsaturated fatty acids: effects on human peripheral blood T lymphocyte proliferation. J Leukoc Biol 1997; 62(4): 438-43.
Gallai V, Sarchielli P, Trequattrini A, et al. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 1995; 56(2): 143-53.
Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989; 320(5): 265-71.
Dworkin RH, Bates D, Millar JH, Paty DW. Linoleic acid and multiple sclerosis: A reanalysis of three double-blind trials. Neurology 1984; 34(11): 1441-5.
Millar JH, Zilkha KJ, Langman MJ, et al. Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. BMJ 1973; 1(5856): 765-8.
Bates D, Fawcett PR, Shaw DA, Weightman D. Trial of polyunsaturated fatty acids in non-relapsing multiple sclerosis. BMJ 1977; 2(6092): 932-3.
Leeming JP, Holland KT, Bojar RA. The in vitro antimicrobial effect of azelaic acid. Br J Dermatol 1986; 115(5): 551-6.
Sieber MA, Hegel JK. Azelaic acid: Properties and mode of action. Skin Pharmacol Physiol 2014; 27(Suppl. 1): 9-17.
Daverat P, Geffard M, Orgogozo JM. Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis. J Neuroimmunol 1989; 22(2): 129-34.
LeVine SM, Chakrabarty A. The role of iron in the pathogenesis of experimental allergic encephalomyelitis and multiple sclerosis. Ann N Y Acad Sci 2004; 1012: 252-66.
Bizzozero OA, DeJesus G, Callahan K, Pastuszyn A. Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis. J Neurosci Res 2005; 81(5): 687-95.
Ljubisavljevic S, Stojanovic I, Cvetkovic T, et al. Erythrocytes’ antioxidative capacity as a potential marker of oxidative stress intensity in neuroinflammation. J Neurol Sci 2014; 337(1-2): 8-13.
van Horssen J, Schreibelt G, Drexhage J, et al. Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med 2008; 45(12): 1729-37.
van Horssen J, Schreibelt G, Bö L, et al. NAD(P)H:quinone oxidoreductase 1 expression in multiple sclerosis lesions. Free Radic Biol Med 2006; 41(2): 311-7.
Witherick J, et al. Mechanisms of Oxidative Damage in Multiple Sclerosis and a Cell Therapy Approach to Treatment. Autoimmune Dis 2011; 2011: 164608.
Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 2004; 251(3): 261-8.
Besler HT, Comoğlu S, Okçu Z. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutr Neurosci 2002; 5(3): 215-20.
Syburra C, Passi S. 1999. Oxidative stress in patients with multiple sclerosis. Ukr Biokhim Zh (1999) 1999; 71(3): 112-5
Ghazavi A, Mosayebi G, Salehi H, Abtahi H. Effect of ethanol extract of saffron (Crocus sativus L.) on the inhibition of experimental autoimmune encephalomyelitis in C57bl/6 mice. Pak J Biol Sci 2009; 12(9): 690-5.
Akhondzadeh S, Sabet MS, Harirchian MH, et al. Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: A 16-week, randomized and placebo-controlled trial. J Clin Pharm Ther 2010; 35(5): 581-8.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy