A new drug candidate (GEMSP) for multiple sclerosis

Current Medicinal Chemistry

Volumn 16, Issue 25, 2009, Pages 3203-3214

  Mangas, Arturo ^a   Coveñas, Rafael ^a   Bodet, Dominique ^b   Duleu, Sebastien ^c   Geffard, Michel ^d  

^a UNIVERSITY OF SALAMANCA   (Spain)

^b Immunochemistry Department   (France)

^c Institut Pour le Developpement de la Recherche en Pathologie Humaine et Therapeutique (IDRPHT)   (France)

^d UNIVERSITÉ BORDEAUX 1   (France)

Author keywords

Autoimmune disease; Brain leukocyte infiltration; Demyelization; Experimental autoimmune encephalomyelitis (EAE); GEMSP; Spinal cord motoneurons

Indexed keywords

AMINO ACID; ANTIINFLAMMATORY AGENT; ANTIOXIDANT; BETA INTERFERON; BETA1A INTERFERON; CARNOSINE; GEMSP; GLATIRAMER; HISTIDINE; INTERFERON BETA SERINE; MELATONIN; METHIONINE; MITOXANTRONE; NATALIZUMAB; NEUROPROTECTIVE AGENT; NEUROTRANSMITTER; PLACEBO; POLYLYSINE; ROQUINIMEX; THIOL DERIVATIVE; UNCLASSIFIED DRUG; VITAMIN;

ABSENCE OF SIDE EFFECTS; ALLERGIC ENCEPHALOMYELITIS; ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANTIBODY PRODUCTION; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ANXIETY; CARDIOTOXICITY; CHEST TIGHTNESS; CHILL; CLINICAL EVALUATION; CLINICAL TRIAL; DEMYELINATION; DEPRESSION; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FEVER; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG RESPONSE; DRUG SAFETY; DRUG SYNTHESIS; DYSPNEA; EVIDENCE BASED PRACTICE; FATIGUE; FLU LIKE SYNDROME; GASTROINTESTINAL DISEASE; HEART ARRHYTHMIA; HEART PALPITATION; HOT FLUSH; HUMAN; IMMUNOCYTOCHEMISTRY; IMMUNOPATHOLOGY; INFECTION; INJECTION SITE REACTION; LEUKOPENIA; LOW DRUG DOSE; LYMPHADENOPATHY; LYMPHOCYTIC INFILTRATION; LYMPHOCYTOPENIA; MALAISE; MENSTRUATION DISORDER; MENTAL DISEASE; MOTONEURON; MULTIPLE SCLEROSIS; MYALGIA; NAUSEA; NEUROPROTECTION; NEUTROPENIA; NONHUMAN; OXIDATIVE STRESS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; REVIEW; SECONDARY AMENORRHEA; SIDE EFFECT; SINGLE DRUG DOSE; SKIN DISEASE; SPASTICITY; SPINAL CORD VENTRAL HORN; TACHYCARDIA; THROMBOCYTOPENIA; TREATMENT DURATION; URINARY TRACT INFECTION;

ANIMALS; DRUG TOXICITY; HUMANS; MULTIPLE SCLEROSIS; POLYLYSINE;

EID: 70450220588     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986709788803259     Document Type: Review

References (73)

1. Calabresi, P.A. Diagnosis and management of multiple sclerosis. Am. Fam. Phys., 2004, 70, 1935-1944
2. Kornek, B.; Storch, M.K.; Weissert, R.; Wallstroem, E.; Stefferl, A.; Olsson, T.; Linnington, C.; Schmidbauer, M.; Lassmann, H. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol., 2000, 157, 267-276 (Pubitemid 30641742)
3. Kieseier, B.C.; Hemmer, B.; Hartung, H-P. Multiple sclerosis-novel insights and new therapeutic strategies. Curr. Opin. Neurol., 2005, 18, 211-220 (Pubitemid 40813745)
4. Fridkis-Hareli, M.; Santambrogio, L.; Stern, J.N.H.; 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
5. Huseby, E.S.; Liggitt, D.; Brabb, T.; Schnabel, B.; Öhlén, C.; Goverman, J. A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J. Exp. Med., 2001, 194, 669-676 (Pubitemid 32844776)
6. Eng, L.F.; Ghirnikar, R.S.; Lee, Y.L. Inflammation in EAE: role of chemokine/cytokine expression by resident and infiltrating cells. Neurochem. Res., 1996, 21, 511-525
7. Benveniste, E.N. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J. Mol. Med., 1997, 75, 165-173 (Pubitemid 27132679)
8. Wiemann, B.; Van, G.Y.; Danilenko, D.M.; Yan, Q.; Matheson, C.; Munyakazi, L.; Ogenstad, S.; Starnes, C.O. Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist. Exp. Neurol., 1998, 149, 455-463
9. Geffard, M.; Bodet, D.; Martinet, Y.; Dabadie, M.P. Intérêt de ĺvaluation d'IgM et IgA spécifiques circulant dans le serum de malades atteints de sclérose en plaques (SEP). Immunoanal. Biol. Spec., 2002, 17, 302-310
10. Bodet, D.; Glaize, G.; Dabadie, M.P.; Geffard, M. Suivi immunobiologique de malades atteints de sclérose en plaques. Immunoanal. Biol. Spec., 2004, 19, 138-147 (Pubitemid 38766006)
11. Mangas, A.; Coveñas, R.; Bodet, D.; Dabadie, M.P.; Glaize, G.; Geffard, M. Evaluation of the effects of a new drug on brain leukocyte infiltration in an experimental model of autoimmune encephalomyelitis. Lett. Drug Des. Discov., 2006, 3, 138-148
12. 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, 150-160 (Pubitemid 351872046)
13. Yu, M.; Nishiyama, A.; Trapp, B.D.; Tuohy, V.K. Interferonbeta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. J. Neuroimmunol., 1996, 64, 91-100. (Pubitemid 26053393)
14. Van der Meide, P.H.; de Labie, M.C.; Ruuls, S.R.; Groenestein, R.J.; Botman, C.A.; Olsson, T.; Dijkstra, C.D. Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms. J. Neuroimmunol., 1998, 84, 14-23.
15. Yasuda, C.L.; Al-Sabbagh, A.; Oliveira, E.C.; Díaz-Bardales, B.M.; García, A.A.; Santos, L.M. Interferon beta modulates experimental autoimmune encephalomyelitis by altering the pattern of cytokine secretion. Immunol. Invest., 1999, 28, 115-126 (Pubitemid 29264192)
16. Floris, S.; Ruuls, S.R.; Wierinckx, A.; van der Pol, S.M.A.; Döpp, E.; van der Meide, P.H.; Dijkstra, C.D.; De Vries, H.E. Interferon- beta directly influences monocyte infiltration into the central nervous system. J. Neuroimmunol., 2002, 127, 69-79. (Pubitemid 34603576)
17. Aharoni, R.; Teitelbaum, D.; Leitner, O.; Meshorer, A.; Sela, M.; Arnon, R. Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1. Proc. Natl. Acad. Sci. USA, 2000, 97, 11472-11477 (Pubitemid 30780919)
18. Teitelbaum, D.; Arnon, R.; Sela, M. Immunomodulation of experimental autoimmune encephalomyelitis by oral administration of copolymer 1. Proc. Natl. Acad. Sci. USA, 1999, 96, 3842-3847 (Pubitemid 29168998)
19. Teitelbaum, D.; Aharoni, R.; Klinger, E.; Kreitman, R.; Raymond, E.; Malley, A.; Shofthi, R.; Sela, M.; Arnon, R. Oral glatiramer acetate in experimental autoimmune encephalomyelitis: clinical and immunological studies. Ann. N. Y. Acad. Sci., 2004, 1029, 239-249 (Pubitemid 40298534)
20. Brunmark, C.; Runström, A.; Ohlsson, L.; Sparre, B.; Brodin, T.; Aström, M.; Hedlund, G. The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2002, 130, 163-172 (Pubitemid 35240003)
21. Karussis, D.M.; Lehmann, D.; Slavin, S.; Vourka-Karussis, U.; Mizrachi-Koll, R.; Ovadia, H.; Ben-Nun, A.; Kalland, T.; Abramsky, O. Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide. Ann. Neurol., 1993, 34, 654-660 (Pubitemid 23333236)
22. Karussis, D.M.; Lehmann, D.; Slavin, S.; Vourka-Karussis, U.; Mizrachi-Koll, R.; Ovadia, H.; Kalland, T.; Abramsky, O. Treatment of chronic-relapsing experimental autoimmune encephalomyelitis with the synthetic immunomodulator linomide (quinoline-3-carboxamide). Proc. Natl. Acad. Sci. USA, 1993, 90, 6400-6404 (Pubitemid 23207220)
23. Lehmann, D.; Karussis, D.M.; Fluresco, D.; Mizrachi-Koll, R.; Ovadia, H.; Shezen, E.; Kalland, T.; Abramsky, O. Immunomodulation of autoimmunity by linomide: inhibition of antigen presentation through down regulation of macrophage activity in the model of experimental autoimmune encephalomyelitis. J. Neuroimmunol., 1997, 74, 102-110. (Pubitemid 27128983)
24. Nguyen, K.B.; McCombe, P.A.; Pender, M.P. Increased apoptosis of T lymphocytes and macrophages in the central and peripheral nervous systems of Lewis rats with experimental autoimmune encephalomyelitis treated with dexamethasone. J. Neuropathol. Exp. Neurol., 1997, 56, 58-69.
25. Noseworthy, J.H.; Lucchinetti, C.F.; Rodríguez, M.; Weinshenker, B.G. Multiple sclerosis. N. Engl. J. Med., 2000, 343, 938-952
26. Arnon, R.; Sela, M. Immunomodulation by the copolymer glatiramer acetate. J. Mol. Recognit., 2003, 16, 412-421
27. Karussis, D.M.; Meiner, Z.; Lehmann, D.; Gomori, J.M.; Schwarz, A.; Linde, A.; Abramsky, O. Treatment of secondary progressive multiple sclerosis with the immunomodulator linomide: a double-blind, placebo-controlled pilot study with monthly magnetic resonance imaging evaluation. Neurology, 1996, 47, 341-346 (Pubitemid 26324025)
28. Noseworthy, J.H.; Wolinsky, J.S.; Lublin, F.D.; Whitaker, J.N.; Linde, A.; Gjörstrup, P.; Sullivan, H.C. Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators. Neurology, 2000, 54, 1726-1733
29. Tan, I.L.; Lycklama à Nijeholt, G.J.; Polman, C.H.; Adèr, H.J.; Barkhof, F. Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials. Mult. Scler., 2000, 6, 99-104.
30. 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. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology, 1995, 45, 1268-1276
31. 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.; Vollmer, T.; Weiner, L.P.; Wolinsky, J.S. Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group. Neurology, 1998, 50, 701-708 (Pubitemid 28146153)
32. Yousry, T.A.; Major, E.O.; Ryschkewitsch, C.; Fahle, G.; Fischer, S.; Hou, J.; Curfman, B.; Miszkiel, K.; Mueller-Lenke, N.; Sanchez, E.; Barkhof, F.; Radue, E.W.; Jäger, H.R.; Clifford, D.B. Evaluation of patients treated with Natalizumab for progressive multifocal leukoencephalopathy. N. Engl. J. Med., 2006, 354, 924-933 (Pubitemid 43313659)
33. Geffard, M.; Tranchant, C.; Fleury, M.; Wiertlewski, S.; Guennoc, A.M.; Dabadie, M.P. GEMSEP1: A new drug candidate for secondary progressive form of multiple sclerosis. Mulp. Scler., 2005, 11(S1), 165.
34. Mangas, A.; Coveñas, R.; Bodet, D.; de León, M.; Duleu, S.; Dabadie, M.P.; Geffard, M. Immunocytochemical localisation of components of GEMSP in the rat CNS after treatment with GEMSP in a chronic EAE model. J. Neurol., 2007, 254 (S3), 104.
35. Weissert, R.; Wallström, E.; Storch, M.K.; Stefferl, A.; Lorentzen, J.; Lassmann, H.; Linington, C.; Olsson, T. MHC haplotypedependent regulation of MOG-induced EAE in rats. J. Clin. Invest., 1998, 102, 1265-1273 (Pubitemid 28436287)
36. Daverat, P.; Geffard, M.; Orgogozo, J.M. Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis. J. Neuroimmunol., 1989, 22, 129-134
37. Boullerne, A.I.; Petry, K.G.; Meynard, M.; Geffard, M. Indirect evidence for nitric oxide involvement in multiple sclerosis by characterization of circulating antibodies directed against conjugated S-nitrosocysteine. J. Neuroimmunol., 1995, 60, 117-124
38. Geffard, M.; Seguela, P.; Heinrich-Rock, AM. Antisera against catecholamines: specificity studies and physicochemical data for anti-dopamine and anti-p-tyramine antibodies. Mol. Immunol., 1984, 21, 515-522
39. Geffard, M.; Kah, O.; Onteniente, B.; Seguela, P.; Le Moal, M.; Delaage, M. Antibodies to dopamine: radioimmunological study of specificity in relation to immunocytochemistry. J. Neurochem., 1984, 42, 1593-1599
40. Seguela, P.; Geffard, M.; Buijs, R.M.; Le Moal, M. Antibodies against gamma-aminobutyric acid: specificity studies and immunocytochemical results. Proc. Natl. Acad. Sci. USA, 1984, 81, 3888-3892 (Pubitemid 14087824)
41. Chagnaud, J.C.; Campistron, G.; Geffard, M. Monoclonal antibody directed against glutaraldehyde conjugated glutamate and immunocytochemical applications in the rat brain. Brain Res., 1989, 481, 175-180 (Pubitemid 19060583)
42. Mangas, A.; Coveñas, R.; Bodet, D.; Geffard, M.; Aguilar, L.A.; Yajeya, J. Immunocytochemical visualization of D-glutamate in the rat brain. Neuroscience, 2007, 144, 654-664 (Pubitemid 44855309)
43. Mangas, A.; Coveñas, R.; Bodet, D.; Geffard, M. In Brain Molecules: from Vitamins to Molecules for Axonal Guidance, Mangas, Coveñas and Geffard, Eds; Transworld Research Network: Trivandrum, 2008; pp. 1-25.
44. Geffard, M.; McRae-Degueurce, A.; Souan, M.L. Immunocytochemical detection of acetylcholine in the rat central nervous system. Science, 1985, 229, 77-79 (Pubitemid 15018284)
45. Geffard, M.; Dulluc, J.; Rock, A.M. Antisera against the indolealkylamines: tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine, 5-methoxytryptophan, and 5-methoxytryptamine tested by an enzyme-linked immunosorbent assay method. J. Neurochem., 1985, 44, 1221-1228
46. Pimm, M.V.; Hudecz, F. Biodistribution in tumour-bearing mice of polycationic, amphoteric and polyanionic branched polypeptides with a poly (L-lysine) backbone labelled with 125I and 111In: tumour accumulation less than that of labelled serum proteins. J. Cancer Res. Clin. Oncol., 1996, 122, 45-54.
47. Ali, M.; Hicks, A.E.; Hellewell, P.G.; Thoma, G.; Norman, K.E. Polymers bearing sLex-mimetics are superior inhibitors of Eselectin-dependent leukocyte rolling in vivo. FASEB J., 2004, 18, 152-154
48. Mangas, A.; Coveñas, R.; Bodet, D.; Duleu, S.; Dabadie, M.P.; Merchán, M.; Geffard, M. In Recent Research Developments in Neuroscience, Pandalai, Ed.; Research Signpost: Trivandrum, 2007; Vol. 2, pp. 93-100.
49. Ryser, H.J.; Shen, W.C. Conjugation of methotrexate to poly (Llysine) increases drug transport and overcomes drug resistance in cultured cells. Proc. Natl. Acad. Sci. USA, 1978, 75, 3867-3870
50. Helgestad, J.; Storm-Mathisen, I.; Lie, S.O. Vitamin C and thiol reagents promote the in vitro growth of murine granulocyte/ macrophage progenitor cells by neutralizing endogenous inhibitor( s). Blut, 1986, 52, 1-8.
51. Iwata-Ichikawa, E.; Kondo, Y.; Miyazaki, I.; Asanuma, M.; Ogawa, N. Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis. J. Neurochem., 1999, 72, 2334-2344 (Pubitemid 29242183)
52. Halliwell, B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant. Physiol., 2006, 141, 312-322 (Pubitemid 43974521)
53. van Meeteren, M.E.; Teunissen, C.E.; Dijkstra, C.D.; van Tol, E.A. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur. J. Clin. Nutr., 2005, 59, 1347-1361 (Pubitemid 43135149)
54. Victor, V.M.; de la Fuente, M. Changes in the superoxide production and other macrophage functions could be related to the mortality of mice with endotoxin-induced oxidative stress. Physiol. Res., 2003, 52, 101-110
55. 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, 261-268 (Pubitemid 38387142)
56. Sano, M.; Ernesto, C.; Thomas, R.G.; Klauber, M.R.; Schafer, K.; Grundman, M.; Woodbury, P.; Growdon, J.; Cotman, C.W.; Pfeiffer, E.; Schneider, L.S.; Thal, L.J. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Engl. J. Med., 1997, 336, 1216-1222
57. Ascherio, A.; Weisskopf, M.G.; O'reilly, E.J.; Jacobs, E.J.; Mc-Cullough, M.L.; Calle, E.E.; Cudkowicz, M.; Thun, M.J. Vitamin E intake and risk of amyotrophic lateral sclerosis. Ann. Neurol., 2005, 57, 104-110
58. Reiter, R.J. Potential biological consequences of excessive light exposure: melatonin suppression, DNA damage, cancer and neurodegenerative diseases. Neuroendocrinol. Lett., 2002, 23, 9-13.
59. Marracci, G.H.; Jones, R.E.; McKeon, G.P.; Bourdette, D.N. Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2002, 131, 104-114
60. Moriya, M.; Nakatsuji, Y.; Okuno, T.; Hamasaki, T.; Sawada, M.; Sakoda, S. Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats. J. Neuroimmunol., 2005, 170, 11-20. (Pubitemid 41740903)
61. Massacesi, L.; Abbamondi, A.L.; Giorgi, C.; Sarlo, F.; Lolli, F.; Amaducci, L. Suppression of experimental allergic encephalomyelitis by retinoic acid. J. Neurol. Sci., 1987, 80, 55-64.
62. Xu, J.; Drew, P.D. 9-Cis-retinoic acid suppresses inflammatory responses of microglia and astrocytes. J. Neuroimmunol., 2006, 171, 135-144
63. Cantorna, M.T. Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? Proc. Soc. Exp. Biol. Med., 2000, 223, 230-233
64. Nashold, F.E.; Hoag, K.A.; Goverman, J.; Hayes, C.E. Rag-1-dependent cells are necessary for 1, 25-dihydroxyvitamin D(3) prevention of experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2001, 119, 16-29.
65. Di Biase, A.; Salvati, S. Exogenous lipids in myelination and myelination. Kaohsiung. J. Med. Sci., 1997, 13, 19-29.
66. Hutter, C.D.; Laing, P. Multiple sclerosis: sunlight, diet, immunology and aetiology. Med. Hypotheses, 1996, 46, 67-74. (Pubitemid 26075766)
67. Darlington, L.G.; Stone, T.W. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br. J. Nutr., 2001, 85, 251-269.
68. Costa, B.; Conti, S.; Giagnoni, G.; Colleoni, M. Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo-oxygenase systems. Br. J. Pharmacol., 2002, 137, 413-420. (Pubitemid 35221894)
69. Althaus, H.H. Remyelination in multiple sclerosis: a new role for neurotrophins? Prog. Brain Res., 2004, 146, 415-432. (Pubitemid 37541397)
70. Pappolla, M.A.; Chyan, Y.J.; Poeggeler, B.; Frangione, B.; Wilson, G.; Ghiso, J.; Reiter, R.J. An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's disease. J. Neural. Transm., 2000, 107, 203-231
71. Teufel, M.; Saudek, V.; Ledig, J.P.; Bernhardt, A.; Boularand, S.; Carreau, A.; Cairns, N.J.; Carter, C.; Cowley, D.J.; Duverger, D.; Ganzhorn, A.J.; Guenet, C.; Heintzelmann, B.; Laucher, V.; Sauvage, C.; Smirnova, T. Sequence identification and characterization of human carnosinase and a closely related nonspecific dipeptidase. J. Biol. Chem., 2003, 278, 6521-6531. (Pubitemid 36800914)
72. Gillson, G.; Wright, J.V.; DeLack, E.; Ballasiotes, G. Transdermal histamine in multiple sclerosis: part one - clinical experience. Altern. Med. Rev., 1999, 4, 424-428 (Pubitemid 30027142)
73. Mangas, A.; Bodet, D.; Coveñas, R.; Geffard, M.; Dabadie, M.P. Evaluation of GEMSP effects on the central nervous system of the Lewis 1a rats in a chronic EAE model. J. Neurol., 2006, 252 (S2), 125.