At the Heart of Elamipretide in Heart Failure

On May 23rd, Brian Stauffer, M.D., cardiologist at the University of Colorado, presented new pre-clinical data examining the effects of elamipretide in human heart cells at Heart Failure 2016 in Florence, Italy.

The heart’s reduced ability to relax and contract during heart failure may be linked to mitochondrial dysfunction and a resulting lack of energy in the heart muscle. Scientists are interested in examining whether elamipretide, which targets mitochondria, may address this lack of energy by restoring mitochondrial function. Two phase 2 clinical trials, PROGRESS-HF and RESTORE-HF, will test the effects of chronic dosing with elamipretide, following last year’s positive results from the single-dose phase 2 PREVIEW trial. But Stauffer’s study is one of the first to examine the effects of elamipretide on heart failure within human tissues.

Clinical trials are critical because they show overall outcomes,” Stauffer said. “But we wanted to look directly in the heart tissue itself to see the influence [of elamipretide].”

Stauffer and team used tissue from collected donated human hearts — end-stage failure hearts being removed during a transplant and healthy donated but unused hearts that served as controls for comparisons. The donations were made at the University of Colorado Anshutz Medical Campus.

As expected, tissue isolated from failing hearts used less oxygen than did tissue from normal hearts, indicating the failing heart tissue also produced less energy.

When the team added elamipretide to the tissue, the failing hearts used significantly more oxygen than before. Normal hearts, on the other hand, did not ramp up activity. The findings are further support for the hypothesis that elamipretide helps damaged mitochondria, without impacting normal, healthy mitochondria.

By teasing apart individual steps in mitochondrial respiration, the group found that elamipretide enhanced energy production by improving the activity of electron transport chain complexes.

Reduced energy in the failing hearts stemmed from abnormalities in the way individual components of the mitochondrial machinery work together in large complexes, according to the study. Treatment with elamipretide once again significantly improved activity in these complexes in failing (but not normal) heart tissue. Stauffer hypothesizes that elamipretide may help bring together pieces of the complex important in early steps of respiration, so that they work more efficiently.

Understanding where respiration falters in failing hearts may help researchers better understand who might respond to treatment with elamipretide. “One of our hopes is that with this human data, we can focus trials better on patients who might benefit most,” Stauffer said.