4.6 Review

The effect of the novel tellurium compound AS101 on autoimmune diseases

Journal

AUTOIMMUNITY REVIEWS
Volume 13, Issue 12, Pages 1230-1235

Publisher

ELSEVIER
DOI: 10.1016/j.autrev.2014.08.003

Keywords

Autoimmune diseases; Tellurium; AS101; Integrins; Cytokines; IL-17

Categories

Funding

  1. Safdie Institute for AIDS and Immunology Research [259108]
  2. Milton and Lois Shiffman Global Research Program [203729]
  3. Dave and Florence Muskovitz Chair in Cancer Research [259099]
  4. Comet Walerstein Cancer Research Program [259124]
  5. Dorsha Wallman Cancer Research Endowment [2959128]

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Tellurium is a rare element, which has been regarded as a non-essential trace element despite its relative abundance in the human body. The chemistry of tellurium supports a plethora of activities, but its biochemistry is not clearly established to date. The small tellurium(IV) compound, ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) developed and initially investigated by us, is currently being evaluated in Phase II clinical trials in psoriasis patients. AS101 is the first tellurium compound to be tested for clinical efficacy. This compound is a potent immunomodulator both in vitro and in vivo with a variety of potential therapeutic applications. The present review will focus on the immunomodulatory properties of AS101, and specifically, its effects in mitigating autoimmune diseases. AS101 has several activities that act on the immune system, including: 1) its ability to reduce IL-17 levels and to inhibit the function of Th17 cells; 2) its specific unique redox-modulating activities enabling the inhibition of specific leukocyte integrins such as alpha 4 beta 1 and alpha 4 beta 7, that are pivotal for diapedesis of macrophages and CD4(+) T inflammatory/auto-reactive cells into the autoimmune tissues; and 3) its ability to enhance the activity of regulatory T cells (Treg). These activities coupled with its excellent safety profile suggest that AS101 may be a promising candidate for the management of autoimmune diseases. (C) 2014 Elsevier B.V. All rights reserved.

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