Therapeutics

S-Equol

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Overview

Name: S-Equol
Synonyms: Aus-131
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: Ausio Pharmaceuticals, LLC

Background

S-Equol is a selective agonist of the estrogen receptor-β, which is expressed on mitochondria. This compound is not a hormone, but rather the S-enantiomeric metabolite of daidzein, a soy-based isoflavone (Setchell et al., 2005). In humans and other mammals, including horses, S-Equol is normally made by intestinal bacteria. This synthesized formulation Aus-131 was originally developed for the treatment of menopausal symptoms and hyperplasia of the prostate.

Unlike estrogen receptor-α, which is expressed in the uterus and breast, ER-β is more strongly expressed in the brain. Estrogen receptor-β is considered a better target for neuroprotection, and agonists of this receptor subtype (SERMs) have been reported to improve hippocampal synaptic function and memory in mice (Tiwari-Woodruff et al., 2007; Feb 2008 news). In cultured rat hippocampal neurons and a mouse ovariectomy model, S-Equol was reported to potentiate mitochondrial function (Yao et al., 2013).

Findings

In July 2015, a Phase 1 study at the University of Kansas Medical Center began enrolling 15 women with very mild or mild AD for a placebo-controlled trial of a six-week course of a twice-daily, 10 mg S-Equol pill or placebo. The primary outcome is activity of the platelet mitochondrial COX enzyme as an indicator of mitochondrial function. 

A separate formulation of three phytoSERMS—S-Equol, daidzein, and genistein—is being evaluated clinically, as well (Dec 2014 conference news; clincialtrials.gov).

For all trials of Aus-131, see clinicaltrials.gov.

Last Updated: 16 Oct 2015

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References

News Citations

  1. Just for Her? Study of Women’s Biology Offers New Therapeutic Angle
  2. Beta Testing—Could Activating Single Estrogen Receptor Boost Memory?

Paper Citations

  1. Setchell KD, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, Wolfe BE, Nechemias-Zimmer L, Brown NM, Lund TD, Handa RJ, Heubi JE. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9. PubMed.
  2. Tiwari-Woodruff S, Morales LB, Lee R, Voskuhl RR. Differential neuroprotective and antiinflammatory effects of estrogen receptor (ER)alpha and ERbeta ligand treatment. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14813-8. PubMed.
  3. Yao J, Zhao L, Mao Z, Chen S, Wong KC, To J, Brinton RD. Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor β-selective phytoSERM treatments. Brain Res. 2013 Jun 13;1514:128-41. Epub 2013 Feb 18 PubMed.

Other Citations

  1. Yao et al., 201

External Citations

  1. clincialtrials.gov
  2. clinicaltrials.gov

Further Reading

Papers

  1. Richardson TE, Simpkins JW. R- and S-equol have equivalent cytoprotective effects in Friedreich's ataxia. BMC Pharmacol Toxicol. 2012 Oct 22;13:12. PubMed.