Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases

Victor Chi, Michael William Pennington, Raymond Stanley Norton, Eric J Tarcha, Luz M Londono, Brian Sims-Fahey, Sanjeev K Upadhyay, Jonathan T Lakey, Shawn Iadonato, Heike Wulff, Christine Beeton, K George Chandy

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157 Citations (Scopus)

Abstract

Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orail + Stim1), TRPM7, Cl-swen-in lymphocytes that initiates and maintains the calcium signaling cascade required for activation. The expression pattern of these channels changes during lymphocyte activation and differentiation, allowing the functional network to adapt during an immune response. The Kv1.3 channel is of interest because it plays a critical role in subsets of T and B lymphocytes implicated in autoimmune disorders. The ShK toxin from the sea anemone Stichodactyla helianthus is a potent blocker of Kv1.3. ShK-186, a synthetic analog of ShK, is being developed as a therapeutic for autoimmune diseases, and is scheduled to begin first-in-man phase-1 trials in 2011. This review describes the journey that has led to the development of ShK-186. (C) 2011 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)529 - 546
Number of pages18
JournalToxicon : official journal of the International Society on Toxinology
Volume59
Issue number4
DOIs
Publication statusPublished - 2012

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