A Sativex®-like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis

British Journal of Pharmacology

Volumn 172, Issue 14, 2015, Pages 3579-3595

  Feliu A ^a,b   Moreno Martet, M ^b,c,d   Mecha, M ^a,b   Carrillo Salinas, F J ^a,b   De Lago, E ^b,c,d   Fernandez Ruiz J ^b,c,d   Guaza, C ^a,b  

^a INSTITUTO CAJAL   (Spain)

^b INSTITUTO RAMÓN Y CAJAL DE INVESTIGACIÓN SANITARIA IRYCIS   (Spain)

^c UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^d CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED SOBRE ENFERMEDADES NEURODEGENERATIVAS CIBERNED   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ARGINASE 1; CANNABIDIOL; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; DRONABINOL; INTERLEUKIN 10; INTERLEUKIN 1BETA; MYELIN; NABIXIMOLS; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEOCHONDROITIN SULFATE; VASCULAR CELL ADHESION MOLECULE 1; PLANT EXTRACT; TETRAHYDROCANNABINOL-CANNABIDIOL COMBINATION;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; ASTROCYTOSIS; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; FEMALE; GENE EXPRESSION; MICROGLIA; MOUSE; MULTIPLE SCLEROSIS; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PRIORITY JOURNAL; SPINAL CORD; THEILER'S MURINE ENCEPHALOMYELITIS VIRUS; UPREGULATION; ANIMAL; COMBINATION DRUG THERAPY; DISEASE COURSE; DISEASE MODEL; DOSE RESPONSE; INBRED MOUSE STRAIN; PATHOGENICITY; PATHOLOGY; THEILOVIRUS; VIROLOGY;

ANIMALS; CANNABIDIOL; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; MICE; MICE, INBRED STRAINS; MULTIPLE SCLEROSIS; PLANT EXTRACTS; THEILOVIRUS;

EID: 84929590521     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13159     Document Type: Article

References (66)

1. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: G Protein-Coupled Receptors. Br J Pharmacol 170: 1459-1581.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: Nuclear Hormone Receptors. Br J Pharmacol 170: 1652-1675.
3. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013c). The Concise Guide to PHARMACOLOGY 2013/14: Enzymes. Br J Pharmacol 170: 1797-1867.
4. Arévalo-Martín A, Vela JM, Molina-Holgado E, Borrell J, Guaza C, (2003). Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J Neurosci 23: 2511-2516.
5. Arévalo-Martín A, García-Ovejero D, Gõmez O, Rubio-Araiz A, Navarro-Galve B, Guaza C, et al. (2008). CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies. Br J Pharmacol 153: 216-225.
6. Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, et al. (2000). Cannabinoids control tremor and spasticity in a multiple sclerosis model. Nature 404: 84-87. 6773.
7. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. (2001). Molecular targets for cannabidiol and its synthetic analogues: effects on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol 134: 845-852.
8. Chang A, Tourtellotte WW, Rudick R, Trapp BD, (2002). Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346: 165-173.
9. Chang A, Staugaitis SM, Dutta R, Batt CE, Easley KE, Chomyk AM, et al. (2012). Cortical remyelination: a new target for repair therapies in multiple sclerosis. Ann Neurol 72: 918-926.
10. Collin C, Davies P, Mutiboko IK, Ratcliffe S, Sativex Spasticity in MS Study Group (2007). Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol 14: 290-296.
11. Compston A, Coles A, (2008). Multiple sclerosis. Lancet 372: 1502-1517.
12. Croxford JL, Miller SD, (2003). Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R + WIN55,212. J Clin Invest 111: 1231-1240.
13. Docagne F, Muñetõn V, Clemente D, Ali C, Loría F, Correa F, et al. (2007). Excitotoxicity in a chronic model of multiple sclerosis: neuroprotective role of cannabinoids through CB1 and CB2 receptor activation. Mol Cell Neurosci 34: 551-561.
14. Esposito G, Scuderi G, Valenza M, Togna GI, Latina V, De Filippis D, et al. (2011). Cannabidiol reduces Ab-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ involvement. PLoS ONE 6: e28668.
15. Feinstein DL, Galea E, Gavrilyuk V, Brosnan CF, Whitacre CC, Dumitrescu-Ozimek L, et al. (2002). Peroxisome proliferator-activated receptor gamma agonists prevent experimental autoimmune encephalomyelitis. Ann Neurol 51: 694-702.
16. Fernández-Ruiz J, García C, Sagredo O, Gõmez-Ruiz M, de Lago E, (2010). The endocannabinoid system as a target for the treatment of neuronal damage. Expert Opin Ther Targets 14: 387-404.
17. Fernández-Ruiz J, Sagredo O, Pazos MR, García RG, Pertwee R, Mechoulam R, et al. (2013). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid. Br J Clin Pharmacol 75: 323-333.
18. Franklin RJM, (2002). Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3: 705-714.
19. García-Merino A, (2013). Endocannabinoid system modulator use in everyday clinical practice in the UK and Spain. Expert Rev Neurother 13: 9-13.
20. Gõmez O, Arevalo-Martin A, Garcia-Ovejero D, Ortega-Gutierrez S, Cisneros JA, Almazan G, et al. (2010). The constitutive production of 2-arachidonoylglycerol participates in oligodendrocyte differentiation. Glia 58: 1913-1927.
21. Goldschmidt T, Antel J, König FB, Brück W, Kuhlmann T, (2009). Remyelination capacity of the MS brain decreases with disease chronicity. Neurology 72: 1914-1921.
22. Gris P, Tighe A, Levin D, Sharma R, Brown A, (2007). Transcriptional regulation of scar gene expression in primary astrocytes. Glia 55: 1145-1155.
23. Haist V, Ulrich R, Kalkuhl A, Deschl U, Baumgartner W, (2012). Distinct spatio-temporal extracellular matrix accumulation within demyelinated spinal cord lesions in Theiler's murine encephalomyelitis. Brain Pathol 22: 188-204.
24. Harlow DE, Macklin WB, (2014). Inhibitors of myelination: ECM changes, CSPGs and PTPs. Exp Neurol 251: 39-46.
25. Haylock-Jacobs S, Keough MB, Lau L, Yong VW, (2011). Chondroitin sulphate proteoglycans: extracellular matrix proteins that regulate immunity of the central nervous system. Autoimmun Rev 10: 766-772.
26. Hurtado A, Podinin H, Oudega M, Grimpe B, (2008). Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord. Brain 131: 2596-2605.
27. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R, (2009). Non-Psychotropic plant cannabinoids: new therapeutic opportunities for an ancient herb. Trends Pharmacol Sci 30: 515-527.
28. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577-1579.
29. Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, Hucke S, et al. (2009). The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell intrinsic fashion and suppresses CNS autoimmunity. J Exp Med 206: 2079-2089.
30. Kozela E, Lev N, Kaushansky N, Eilam R, Rimmerman N, Levy R, et al. (2011). Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol 163: 1507-1519.
31. Lau LW, Keough MB, Haylock-Jacobs S, Cua R, Döring A, Sloka S, et al. (2012). Chondroitin sulfate proteoglycans in demyelinated lesions impair demyelination. Ann Neurol 72: 419-432.
32. Lipton HL, Dal Canto MC, (1976). Chronic neurologic disease in Theiler's virus infection of SJL/J mice. J Neurol Sci 30: 201-207.
33. Lledõ A, Borrell J, Guaza C, (1999). Dexamethasone regulation of interleukin-1 receptors in the hippocampus of Theiler's virus infected mice: effects on virus-mediated demyelination. Eur J Pharmacol 372: 75-83.
34. Loría F, Petrosino S, Hernangõmez M, Mestre L, Spagnolo A, Correa F, et al. (2010). An endocannabinoid tone limits excitotoxicity in vitro and in a model of multiple sclerosis. Neurobiol Dis 37: 166-176.
35. Lyman WD, Sonett JR, Brosnan CF, Elkin R, Bornstein MB, (1989). Delta 9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J Neuroimmunol 23: 73-81.
36. Malfait AM, Gallily R, Sumariwalla PF, Malik AS, Andreakos E, Mechoulam R, et al. (2000). The non-psychotropic cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 97: 9561-9566.
37. Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, et al. (2007). Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 13: 492-497.
38. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, et al. (2003). CB1 cannabinoid receptors and on demand defense against excitotoxicity. Science 302: 84-88.
39. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
40. Mecha M, Iñigo PM, Mestre L, Hernangõmez M, Borrel J, Guaza C, (2011). An easy and fast way to obtain a high number of glial cells from rat cerebral tissue: a beginners approach. Protoc Exch. doi: 10.1038/protex.2011.218
41. Mecha M, Torrao AS, Mestre L, Carrillo-Salinas FJ, Mechoulam R, Guaza C, (2012). Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress. Cell Death Dis 3: e331.
42. Mecha M, Carrillo-Salinas FJ, Feliu A, Guaza C, (2013a). Viral models of multiple sclerosis: neurodegeneration and demyelination in mice infected with Theiler's virus. Prog Neurobiol 102: 46-64.
43. Mecha M, Feliú A, Iñigo PM, Mestre L, Carrillo-Salinas FJ, Guaza C, (2013b). Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: a role for A2A receptors. Neurobiol Dis 59: 141-150.
44. Mestre L, Docagne F, Correa F, Loría F, Hernangõmez M, Borrell J, et al. (2009). A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulation the adhesion molecules. Mol Cell Neurosci 40: 258-266.
45. Miller SD, Vanderlugt CL, Begolka WS, Pao W, Yauch RL, Neville KL, et al. (1997). Persistent infection with TMEV leads to CNS autoimmunity via epitope spreading. Nat Med 3: 1133-1136.
46. Mohan H, Krumbholz M, Sharma R, Eisele S, Junker A, Sixt M, et al. (2010). Extracellular matrix in multiple sclerosis lesions: fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells. Brain Pathol 20: 966-975.
47. Molina-Holgado E, Vela JM, Arévalo-Martín A, Almazán G, Molina-Holgado F, Borrell J, et al. (2002). Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22: 9742-9753.
48. Moreno-Martet M, Espejo-Porras F, Fernández-Ruiz J, de Lago E, (2014). Changes in endocannabinoid receptors and enzymes in the spinal cord of SOD1G93A transgenic mice and evaluation of a Sativex®-like combination of phytocannabinoids: interest for future therapies in amyotrophic lateral sclerosis. CNS Neurosci Ther 20: 809-815.
49. Nash B, Ioannidou K, Barnett SC, (2011). Astrocyte phenotypes and their relationship to myelination. J Anat 219: 44-52.
50. O'Sullivan SE, Kendall DA, (2010). Cannabinoid activation of peroxisome proliferator-activated receptors: potential for modulation of inflammatory disease. Immunobiology 215: 611-616.
51. Pawson AJ, Sharman JL, Benson HE, Faccenda E, Alexander SP, Buneman OP, et al.; NC-IUPHAR. (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledge base of drug targets and their ligands. Nucl Acids Res 42 (Database Issue): D1098-D1106.
52. Pendleton JC, Shamblott MJ, Gary DS, Belegu V, Hurtado A, Malone ML, et al. (2013). Chondroitin sulfate proteoglycans inhibit oligodendrocyte myelination through PTPσ. Exp Neurol 247: 113-121.
53. Pryce G, Baker D, (2012). Potential control of multiple sclerosis by cannabis and the endocannabinoid system. CNS Neurol Disord Drug Targets 11: 624-641.
54. Pryce G, Ahmed Z, Hankey DJ, Jackson SJ, Croxford JL, Pocock JM, et al. (2003). Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126: 2191-2202.
55. Sastre-Garriga J, Vila C, Clissold S, Montalban X, (2011). THC and CBD oromucosal spray (Sativex®) in the management of spasticity associated with multiple sclerosis. Expert Rev Neurother 11: 627-637.
56. Serpell MG, Notcutt W, Collin C, (2013). Sativex long-term use: an open-label trial study in patients with spasticity due to multiple sclerosis. J Neurol 260: 285-295.
57. Siebert JR, Osterhout DJ, (2011). The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes. J Neurochem 119: 176-188.
58. Silver J, Miller JH, (2004). Regeneration beyond the glial scar. Nat Rev Neurosci 5: 146-156.
59. Sisay S, Pryce G, Jackson SJ, Tanner C, Ross RA, Michael GJ, et al. (2013). Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis. PLoS ONE 8: e76907.
60. Sobel RA, Ahmed AS, (2001). White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. J Neuropathol Exp Neurol 60: 1198-1207.
61. Susarla BT, Laing ED, Yu P, Katagiri Y, Geller HM, Symes AJ, (2011). Smad proteins differentially regulate transforming growth factor-β-mediated induction of chondroitin sulfate proteoglycans. J Neurochem 119: 868-878.
62. Ulrich R, Seeliger F, Kreutzer M, Germann PG, Baumgärtner W, (2008). Limited remyelination in Theiler's murine encephalomyelitis due to insufficient oligodendroglial differentiation of nerve/glial antigen 2 (NG2)-positive putative oligodendroglial progenitor cells. Neuropathol Appl Neurobiol 34: 603-620.
63. Valdeolivas S, Satta V, Pertwee RG, Fernández-Ruiz J, Sagredo O, (2012). Sativex like combination of phytocannabinoids is neuroprotective in malonate-lesioned rats, an inflammatory model of Hungtinton's disease: role of CB1 and CB2 receptors. ACS Chem Neurosci 3: 400-406.
64. Velayudhan L, Van Diepen E, Marudkar M, Hands O, Suribhatla S, Prettyman R, et al. (2014). Therapeutic potential of cannabinoids in neurodegenerative diseases: a selective review. Curr Pharm Des 20: 2218-2230.
65. Wade DT, Collin C, Stott C, Duncombe P, (2010). Meta-analysis of the efficacy of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler 16: 707-714.
66. Zajicek J, Ball S, Wright D, Vickery J, Nunn A, Miller D, et al. (2013). Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial. Lancet Neurol 12: 857-865.