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

Victor Chi, Michael W. Pennington, Raymond S. 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

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Electrophysiological and pharmacological studies coupled with molecular identification have revealed a unique network of ion channels-Kv1.3, KCa3.1, CRAC (Orai1 + Stim1), TRPM7, Cl swell-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.

Original languageEnglish (US)
Pages (from-to)529-546
Number of pages18
JournalToxicon
Volume59
Issue number4
DOIs
StatePublished - Mar 15 2012

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Sea Anemones
B-Lymphocyte Subsets
Calcium Signaling
Lymphocytes
Helianthus
Immunologic Factors
T-Lymphocyte Subsets
Lymphocyte Activation
Ion Channels
Autoimmune Diseases
Pharmacology
Chemical activation
Therapeutics
Calcium
ShK neurotoxin

Keywords

  • Autoimmune
  • B cell
  • BgK
  • CRAC
  • KCa3.1
  • Kv1.3
  • Multiple sclerosis
  • PAP-1
  • Potassium channel
  • Psoriasis
  • Rheumatoid arthritis
  • Sea anemone
  • ShK
  • ShK-186
  • ShK-192
  • T cell
  • Toxin
  • Transplant
  • Type-1 diabetes mellitus

ASJC Scopus subject areas

  • Toxicology

Cite this

Chi, V., Pennington, M. W., Norton, R. S., Tarcha, E. J., Londono, L. M., Sims-Fahey, B., ... Chandy, K. G. (2012). Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. Toxicon, 59(4), 529-546. https://doi.org/10.1016/j.toxicon.2011.07.016

Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. / Chi, Victor; Pennington, Michael W.; Norton, Raymond S.; Tarcha, Eric J.; Londono, Luz M.; Sims-Fahey, Brian; Upadhyay, Sanjeev K.; Lakey, Jonathan T.; Iadonato, Shawn; Wulff, Heike; Beeton, Christine; Chandy, K. George.

In: Toxicon, Vol. 59, No. 4, 15.03.2012, p. 529-546.

Research output: Contribution to journalArticle

Chi, V, Pennington, MW, Norton, RS, Tarcha, EJ, Londono, LM, Sims-Fahey, B, Upadhyay, SK, Lakey, JT, Iadonato, S, Wulff, H, Beeton, C & Chandy, KG 2012, 'Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases', Toxicon, vol. 59, no. 4, pp. 529-546. https://doi.org/10.1016/j.toxicon.2011.07.016
Chi V, Pennington MW, Norton RS, Tarcha EJ, Londono LM, Sims-Fahey B et al. Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. Toxicon. 2012 Mar 15;59(4):529-546. https://doi.org/10.1016/j.toxicon.2011.07.016
Chi, Victor ; Pennington, Michael W. ; Norton, Raymond S. ; Tarcha, Eric J. ; Londono, Luz M. ; Sims-Fahey, Brian ; Upadhyay, Sanjeev K. ; Lakey, Jonathan T. ; Iadonato, Shawn ; Wulff, Heike ; Beeton, Christine ; Chandy, K. George. / Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. In: Toxicon. 2012 ; Vol. 59, No. 4. pp. 529-546.
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