Therapeutics

S-Equol

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., 2007Feb 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 newsclincialtrials.gov).

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

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