The natural antioxidant epicatechin significantly improves heart structure and function in young people with Friedreich’s ataxia (FA) over nearly six months of treatment, a small Phase 2 study has shown.
The findings support the need for larger trials that include control groups to establish whether epicatechin can maintain these benefits, scientists said.
FA is caused by mutations in the FXN gene, which carries instructions for producing a protein called frataxin. This protein is essential for the normal functioning of small energy-producing structures in the cells known as mitochondria. A lack of frataxin leads to mitochondrial malfunction and to oxidative stress — when the body’s antioxidant defenses are not able to protect against oxidative damage — inducing FA’s clinical symptoms.
This compound exists in two identical but mirror-image forms: (+)-epicatechin and (-)-epicatechin.
In animal models, (-)-epicatechin improved cardiac structure and function, eased oxidative stress, and induced regeneration of nerve cells. In clinical trials, (-)-epicatechin promoted mitochondrial growth and function, and improved skeletal muscle regeneration.
Recent research has suggested that the other form, (+)-epicatechin, may be more potent and longer-lasting than (-)-epicatechin. A Phase 1 pilot study (NCT02330276) in 12 healthy individuals and people with prediabetes suggested that (+)-epicatechin is safe.
Based on these results, a Phase 2 study (NCT02660112) was conducted to test the safety and effectiveness of (+)-epicatechin in young people with FA.
Ten patients were selected, ages 10 to 22. Mean disease duration was 4.5 years.
Participants received one 25 mg capsule of (+)-epicatechin, taken orally three times per day (75 mg daily) for 12 weeks. Five patients without improvements had doses increased to two 25 mg capsules three times per day (150 mg daily). All patients were treated for 24 weeks in total, or almost six months.
Primary neurological goals were changes from baseline (study start) to 12 and 24 weeks in the Friedreich’s Ataxia Rating Scale (FARS), which is a measure of disease progression. An eight-meter timed walk measured neuromuscular ability.
After 12 and 24 weeks, overall FARS score improved, but did not reach statistical significance compared to baseline. A measure of spinal cord integrity did not show improvements either.
Still, five participants showed score improvements, three experienced benefits assessed with the eight-meter walk, and six had improvements in the nine-hole peg test of finger dexterity.
At 12 weeks, no differences emerged in blood pressure or heart rate compared to baseline. At 24 weeks, treatment led to a significant reduction in diastolic blood pressure (when the heart is relaxed), but not in systolic blood pressure, when the heart is pumping.
Cardiac MRI showed a significant reduction (improvement) in the mass of the left ventricle at 12 weeks, but not at the end of the study. Mean ejection fraction of the left ventricle, which refers to the amount of blood pumped out with each heartbeat, was unchanged at 12 weeks but increased significantly at 24 weeks.
Echocardiograms showed no changes except for the thickness of the wall dividing the right and left side of the heart, which increased (worsened) by 1.3 millimeters at 24 weeks.
No serious adverse events (side effects) or hospitalizations were reported. Three patients experienced nausea and dizziness, which did not affect daily activities. Compounds such as (+)-epicatechin are known to affect blood clotting; however, no impact on blood platelets was found.
“[(+)-epicatechin] is safe and well tolerated over 24 weeks of treatment in [FA] subjects and resulted in notable improvements in cardiac structure and function in subset of patients,” the scientists wrote.
“This study may serve as a milestone for large controlled trials of longer duration to establish whether [(+)-epicatechin] sustains positive effect on MRI derived cardiac mass and systolic function in patients with mitochondrial disease,” they added.
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