Autoimmune disease

Disease ID:105
Name:Autoimmune disease
Associated with:1 target
Synonyms
hypersensitivity reaction disease
Database Links
Disease Ontology: DOID:0060056
OMIM: 109100, 126200, 177900, 222100, 604302

Targets

Kv1.3
Role:  Associated with Multiple-Sclerosis, Type -1 Diabetes, Rheumatoid Arthritis and Psoriasis.
Kv1.3 expression is increased in activated CCR7-effector memory T-cells. Blockers of this channel potently inhibit proliferation and cytokine secretion of effector memory T cells and have little or no effect on naive and central memory T-cells.
Drugs:  Kaliotoxin treats experimental autoimmune encephalomyelitis (EAE) and bone resorption in experimental periodontal disease in rats.
PAP-1 prevents experimental autoimmune diabetes and will suppress allergic contact dermatitis in rats.
margatoxin suppresses delayed-type hypersensitivity in pigs.
Side effects:  Inhibition of effector memory T-cells could potentially lead to reactivation of viral infections such as CMV.
Therapeutic use:  ShK derivative and PAP-1 are in clinical development
Comments:  Kv1.3 blockers are potentially useful for treating autoimmune diseases where terminally differentiated effector memory T cells are involved in pathogenesis.
References:  1-6

Ligands

No ligand related data available for Autoimmune disease

References

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1. Beeton C, Barbaria J, Giraud P, Devaux J, Benoliel AM, Gola M, Sabatier JM, Bernard D, Crest M, Béraud E. (2001) Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation. J. Immunol., 166 (2): 936-44. [PMID:11145670]

2. Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, Cahalan MD, Chandy KG, Béraud E. (2001) Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Proc. Natl. Acad. Sci. U.S.A., 98 (24): 13942-7. [PMID:11717451]

3. Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, Kolski-Andreaco A, Wei E, Grino A, Counts DR, Wang PH, LeeHealey CJ, S Andrews B, Sankaranarayanan A, Homerick D, Roeck WW, Tehranzadeh J, Stanhope KL, Zimin P, Havel PJ, Griffey S, Knaus HG, Nepom GT, Gutman GA, Calabresi PA, Chandy KG. (2006) Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc. Natl. Acad. Sci. U.S.A., 103 (46): 17414-9. [PMID:17088564]

4. Koo GC, Blake JT, Talento A, Nguyen M, Lin S, Sirotina A, Shah K, Mulvany K, Hora D, Cunningham P, Wunderler DL, McManus OB, Slaughter R, Bugianesi R, Felix J, Garcia M, Williamson J, Kaczorowski G, Sigal NH, Springer MS, Feeney W. (1997) Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses in vivo. J. Immunol., 158 (11): 5120-8. [PMID:9164927]

5. Valverde P, Kawai T, Taubman MA. (2004) Selective blockade of voltage-gated potassium channels reduces inflammatory bone resorption in experimental periodontal disease. J. Bone Miner. Res., 19 (1): 155-64. [PMID:14753747]

6. Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C, Chandy KG. (2003) The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS. J. Clin. Invest., 111 (11): 1703-13. [PMID:12782673]