Treatment of chronic relapsing-remitting EAE in rats with ShK-186, an inhibitor of Kv1.3 channels in effector memory T cells.
Matheu MP, Beeton C, Garcia A, Chi V, Rangaraju S, Safrina O, Monaghan K, Uemura MI, Li D, Pal S, de la Maza LM, Monuki E, Flügel A, Pennington MW, Parker I, Chandy KG, Cahalan MD.
Department of Physiology and Biophysics, University of California Irvine
This video shows three Dark Agouti (DA) rats with chronic relapsing-remitting experimental autoimmune encephalomyelitis (CR-EAE) that have been treated for 30 days with the Kv1.3 channel-specific blocker ShK-186. CR-EAE was induced by spinal cord homogenate in complete Freund's adjuvant. Disease began about 10 days later. In the accompanying video, these three rats were shown at the onset of disease. In this video we show the efficacy of treatment with ShK-186, We began treatment at the onset of disease (score of 1.0 = limp tail). ShK-186 was administered once daily by subcutaneous injection (100 ug/kg). The rats have recovered from the disease. Other rats administered saline once daily by subcutaneous injection did not recover (Matheu et al, Immunity 2008; 29:602-14).
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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. Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17414-9.
Matheu MP, Beeton C, Garcia A, Chi V, Rangaraju S, Safrina O, Monaghan K, Uemura MI, Li D, Pal S, de la Maza LM, Monuki E, Flügel A, Pennington MW, Parker I, Chandy KG, Cahalan MD. Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. Immunity. 2008 Oct;29(4):602-14.
Beeton C, Garcia A, Chandy KG. Induction and clinical scoring of chronic-relapsing experimental autoimmune encephalomyelitis. J Vis Exp. 2007;(5):224. Epub 2007 Jul 4.
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