Epicatechin for Friedreich’s ataxia

Last updated Nov. 7, 2023, by José Lopes, PhD
Fact-checked by Patrícia Silva, PhD

What is epicatechin for Friedreich’s ataxia?

Epicatechin is a naturally occurring compound explored by Epirium Bio (formerly Cardero Therapeutics) and investigators at Mayo Clinic as a potential treatment to improve cardiac and neurological function in Friedreich’s ataxia (FA).

Epicatechin belongs to a group of molecules called flavonols, which are found in a variety of fruits and vegetables, as well as red wine and tea. Flavonols have been reported to have antioxidant effects and lower the risk of vascular disease.

The compound can be found as (+)-epicatechin and (-)-epicatechin, two enantiomers. This means that the two forms are nonsuperimposable mirror images of each other.

Therapy snapshot

How does epicatechin work in FA?

FA is caused by mutations in the FXN gene, which codes for a protein called frataxin. This protein is important for the normal functioning of mitochondria, the energy factories of cells. The lack of frataxin leads to a progressive impairment of muscle coordination (known as ataxia), loss of muscle strength and sensation, and impaired speech, vision, and hearing.

(-)-Epicatechin has been reported to have antioxidant properties and a cardioprotective action. Structural and metabolic effects in muscle have also been shown. Studies in animals and people indicated better mitochondrial function and improved muscle regeneration.

Studies have shown that (+)-epicatechin is more potent than (-)-epicatechin in inducing mitochondrial formation and improving cardiac and metabolic measures.

How will epicatechin be administered in FA?

(+)-Epicatechin was tested in a Phase 2 clinical trial with FA patients as oral tablets given over 24 weeks, nearly six months. The total daily dose was 75 mg, divided in three 25 mg capsules per day.

Epicatechin in clinical trials

A Phase 1 clinical trial (NCT02330276) tested the safety and pharmacological properties of (+)-epicatechin in 12 participants. Participants were healthy volunteers and people with pre-diabetes, as defined by the criteria of the American Diabetes Association that included a body mass index (a measure of body fat) higher than 27 kg per square meter, impaired fasting glucose at 100-125 mg/dL, and elevated HbA1c, a standard marker of diabetes risk.

(+)-Epicatechin was given orally at 10, 30, or 100 mg when assessing how the compound moves into, through, and out of the body (a parameter called pharmacokinetics), and at 30 mg daily for seven days when evaluating its effects on the body (pharmacodynamics).

Results showed that (+)-epicatechin was well tolerated, with no side effects being reported. Blood levels of TNF-alpha and MCP-1, two proteins implicated in inflammation, were lower during treatment though the difference was not statistically significant.

On the basis of these findings, a Phase 2 study (NCT02660112) tested the safety and effectiveness of (+)-epicatechin in FA patients with up to seven years of disease duration. The trial had 10 participants, ages 10 to 22.

(+)-Epicatechin was administered as oral capsules at 75 mg per day for 24 weeks (almost six months), with an increase to 150 mg per day at 12 weeks for participants not showing improvements.

Results showed significantly better cardiac function with treatment, as assessed by mean left ventricular ejection fraction — the amount of blood pumped out by the heart’s left ventricle with each heartbeat. Other measures of cardiac function and structure did not change significantly.

Friedreich’s Ataxia Rating Scale (FARS) scores, a measure of neurological impairment, improved in five patients; whereas the 8-meter test of walking speed showed benefits in three participants, and the 9-peg hole test of finger dexterity improved in six. However, the overall mean scores of these tests were not significantly different. Levels of follistatin, a muscle regeneration biomarker, were significantly increased.

In addition, (+)-epicatechin was safe and well tolerated, without significant adverse events or hospitalizations. Three participants experienced a temporary increase in migraine-associated symptoms, namely nausea and dizziness, that did not affect daily activities or made them stop treatment.

Common side effects of epicatechin

In a Phase 2 study in FA patients, results showed a temporary increase in nausea and dizziness in some patients, but this did not affect daily activities or lead to treatment discontinuation.

Friedreich’s Ataxia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.