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