S-equol (also known as AUS-131) is an oral medicine initially developed by Cincinnati-based Ausio Pharmaceuticals for treating the symptoms of menopause and benign prostate hyperplasia (BPH). It  now is being investigated for its potential to treat mitochondrial dysfunction in Alzheimer’s disease.

How S-equol works

Brain cells need high energy stores in order to function optimally. This energy is supplied by the mitochondria, which house cytochrome oxidase, a key enzyme that enables them to do their job. Faulty mitochondria have been observed in Alzheimer’s, and are thought to contribute to amyloid-beta plaque deposits in nerve cells, a hallmark of the disease, ultimately leading to nerve cell death.

The estrogen hormone (a chemical typically linked with the reproductive system) can create new mitochondria and enhance their activity by binding to estrogen receptor-beta found on the surface of the mitochondria. S-equol works by binding to these same estrogen receptors, activating them, and therefore improving mitochondrial function.

S-equol is a soy-derivative; it is not a hormone or steroid.

S-equol in clinical trials for Alzheimer’s disease

S-equol was reported to promote mitochondrial function in rats and cultured brain cells.

A Phase 1 clinical trial (NCT02142777) called SEAD was performed in 15 patients with very mild to mild Alzheimer’s disease to determine whether S-equol was able to improve mitochondrial activity. Participants were given a twice-daily placebo treatment for two weeks, followed by 10 mg of S-equol twice daily for two weeks, and then two weeks of no treatment.

The results showed that S-equol was able to increase the activity of cytochrome oxidase (a marker of mitochondrial function) and was safe and well-tolerated in all trial participants. This trial was a collaborative effort between Ausio Pharmaceuticals and the University of Kansas Medical Center Research Institute. It was led by Russell Swerdlow, MD, and took place from July 2014 to April 2016.

SEAD2, a Phase 1/2 clinical trial (NCT03101085), was launched in May 2017.  It is recruiting up to an estimated 40 participants with Alzheimer’s disease at the University of Kansas Medical Center and its Clinical and Translational Science Unit. The patients will be divided into two groups with one group receiving 50 mg of S-equol twice daily, and the other receiving placebo pills for a month. Researchers aim to investigate S-equol’s effect on cytochrome oxidase activity, various cognitive skills, and its safety profile. The trial is set to end in October 2019.

Further details

S-equol also is being investigated for potential treatment of other conditions such as high blood pressure (NCT02515682), BPH (NCT00962390), menopause (NCT00962585), breast cancer (NCT02352025), and acne vulgaris (NCT01301586).


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