Multiple sclerosis

Disease ID:648
Name:Multiple sclerosis
Associated with:9 targets
2 immuno-relevant targets
6 immuno-relevant ligands
Database Links
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802

Targets

GPR17
Role:  GPR17 upregulation appears to be associated with demyelinating lesions induced by experimental autoimmune encephalomyelitis and multiple sclerosis
References:  4
BLT1 receptor
References:  9
Nav1.8
Role:  Nav mRNA and protein are upregulated within cerebellar Purkinje neurons in both humans and mouse models of multiple sclerosis, where they may produce abnormal patterns of firing which may be contributing to ataxia.
References:  3,14-15
MMP9
Comments:  MMP9 is upregulated in cerebrospinal fluid (CSF), blood and brain tissue of MS patients, can be a useful biomarker and expression level is reduced in response to MS treatment with interferon beta.
CIITA
BAFF receptor
Comments:  The anti-BAFF-R mAb VAY736 has completed Phase 2 clinical evaluation in RRMS- see NCT02038049.
programmed cell death 1 (CD279)
regulator of G-protein signaling 1
References:  7-8,11,16
repulsive guidance molecule BMP co-receptor a
References:  12

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
IFN-β1b (recombinant human)
Immuno Disease Comments: Approved drug for relapsing forms of MS.
Clinical Use: Like , IFN-β1b is used to treat relapsing forms of multiple sclerosis [6,10]. | View clinical data
natalizumab
Immuno Disease Comments: Approved for the treatment of relapsing forms of multiple sclerosis.
Clinical Use: Used in the treatment of relapsing forms of multiple sclerosis, and in the management of Crohn's disease. However, natalizumab is not widely prescribed due to safety concerns around progressive multifocal leukoencephalopathy (PML). | View clinical data
Bioactivity Comments: We have been unable to find affinity data for this antibody from an open access article. | View biological activity
ACTH
Immuno Disease Comments: A corticotropin used to treat the symptoms of many inflammatory disorders including MS.
Clinical Use: Corticotropin is used to treat the symptoms of many allergic disorders, psoriasis and other skin conditions, eye conditions, arthritis, lupus, multiple sclerosis, ulcerative colitis and breathing disorders, for example. This peptide is also used to diagonse adrenocortical insufficiency. | View clinical data
Bioactivity Comments: Although we have recorded affinity data for ACTH at melanocortin receptors 1, 3, 4 and 5, affinity data for the human melanocortin receptor 2, the peptide's primary target, is lacking. As a peptide mimetic of ACTH we would expect corticotropin to have similar affinities to the endogenous peptide. | View biological activity
IL-17A
Immuno Disease Comments: Approved therapy for MS.
ROMe
Immuno Disease Comments: A synthetic sphingosine analogue that inhibits sphingosine kinase 2 and has shown efficacy in a rodent model of MS.
dimethyl fumarate 5
Immuno Disease Comments: Approved drug for relapsing MS. The effect of DMF on innate and adaptive immunity in MS is discussed by Diebold et al. (2018)
Clinical Use: Dimethylf fumarate is an anti-inflammatory drug used to treat patients with relapsing multiple sclerosis. In June 2017 the EMA approved dimethyl fumarate (Skilarence®) as a treatment for plaque psoriasis. | View clinical data
Bioactivity Comments: As this compound is a prodrug it may have little or no measurable bioactivity at the molecular target of its active counterpart. Therefore, we have not tagged a primary drug target. | View biological activity

References

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1. Anthony DC, Ferguson B, Matyzak MK, Miller KM, Esiri MM, Perry VH. (1997) Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol., 23 (5): 406-15. [PMID:9364466]

2. Benesová Y, Vasku A, Novotná H, Litzman J, Stourac P, Beránek M, Kadanka Z, Bednarík J. (2009) Matrix metalloproteinase-9 and matrix metalloproteinase-2 as biomarkers of various courses in multiple sclerosis. Mult Scler., 15 (3): 316-22. [PMID:19153173]

3. Black JA, Dib-Hajj S, Baker D, Newcombe J, Cuzner ML, Waxman SG. (2000) Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A., 97 (21): 11598-602. [PMID:11027357]

4. Chen Y, Wu H, Wang S, Koito H, Li J, Ye F, Hoang J, Escobar SS, Gow A, Arnett HA, Trapp BD, Karandikar NJ, Hsieh J, Lu QR. (2009) The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nat. Neurosci., 12 (11): 1398-406. [PMID:19838178]

5. Diebold M, Sievers C, Bantug G, Sanderson N, Kappos L, Kuhle J, Lindberg RLP, Derfuss T. (2018) Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis. J. Autoimmun., 86: 39-50. [PMID:28958667]

6. Freedman MS. (2014) Evidence for the efficacy of interferon beta-1b in delaying the onset of clinically definite multiple sclerosis in individuals with clinically isolated syndrome. Ther Adv Neurol Disord, 7 (6): 279-88. [PMID:25371710]

7. International Multiple Sclerosis Genetics Conssortium (IMSGC). (2010) IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun., 11 (5): 397-405. [PMID:20555355]

8. Johnson BA, Wang J, Taylor EM, Caillier SJ, Herbert J, Khan OA, Cross AH, De Jager PL, Gourraud PA, Cree BC et al.. (2010) Multiple sclerosis susceptibility alleles in African Americans. Genes Immun., 11 (4): 343-50. [PMID:19865102]

9. Kihara Y, Yokomizo T, Kunita A, Morishita Y, Fukayama M, Ishii S, Shimizu T. (2010) The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis. Biochem. Biophys. Res. Commun., 394 (3): 673-8. [PMID:20226760]

10. Marziniak M, Meuth S. (2014) Current perspectives on interferon Beta-1b for the treatment of multiple sclerosis. Adv Ther, 31 (9): 915-31. [PMID:25182864]

11. Mowry EM, Carey RF, Blasco MR, Pelletier J, Duquette P, Villoslada P, Malikova I, Roger E, Kinkel RP, McDonald J et al.. (2013) Multiple sclerosis susceptibility genes: associations with relapse severity and recovery. PLoS ONE, 8 (10): e75416. [PMID:24130709]

12. Nohra R, Beyeen AD, Guo JP, Khademi M, Sundqvist E, Hedreul MT, Sellebjerg F, Smestad C, Oturai AB, Harbo HF et al.. (2010) RGMA and IL21R show association with experimental inflammation and multiple sclerosis. Genes Immun., 11 (4): 279-93. [PMID:20072140]

13. Rahmanzadeh R, Weber MS, Brück W, Navardi S, Sahraian MA. (2018) B cells in multiple sclerosis therapy-A comprehensive review. Acta Neurol. Scand., 137 (6): 544-556. [PMID:29512131]

14. Renganathan M, Gelderblom M, Black JA, Waxman SG. (2003) Expression of Nav1.8 sodium channels perturbs the firing patterns of cerebellar Purkinje cells. Brain Res., 959 (2): 235-42. [PMID:12493611]

15. Saab CY, Craner MJ, Kataoka Y, Waxman SG. (2004) Abnormal Purkinje cell activity in vivo in experimental allergic encephalomyelitis. Exp Brain Res, 158 (1): 1-8. [PMID:15118796]

16. Tran T, Paz P, Velichko S, Cifrese J, Belur P, Yamaguchi KD, Ku K, Mirshahpanah P, Reder AT, Croze E. (2010) Interferonβ-1b Induces the Expression of RGS1 a Negative Regulator of G-Protein Signaling. Int J Cell Biol, 2010: 529376. [PMID:21274427]

17. Yong VW, Zabad RK, Agrawal S, Goncalves Dasilva A, Metz LM. (2007) Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators. J Neurol Sci., 259: 79-84. [PMID:17382965]