Tests on large animal models have shown success in reversing heart failure through the use of powerful gene therapy, delivered straight to the heart.

The new model of therapy employs a gene that’s otherwise “missing in action” among heart failure patients. Known as SUMO-1, the gene plays a key role in cardiac function because it helps regulate calcium homeostasis in heart cells. A reduction in SUMO-1 destabilizes calcium’s effect on the heart’s ability to contract and relax, making efficient pumping action belabored, or even impossible. Published in Science Translational Medicine, the present study uses SUMO-1 in conjunction with another cardiac protein, SERCA2, in an attempt to fully reverse heart failure.

Heart failure results from a heart that can no longer pump enough blood throughout the body. A number of resulting symptoms can arise, such as shortness of breath, weakened contractions, and an enlargement of the ventricles. Heart failure affects roughly 5.7 million people in the United States, most commonly the elderly. The condition may require a range of treatment, depending on the severity: doctors may tell patients with moderate cases simply to exercise more or to change their diets, while more severe cases could require implanted devices or even a heart transplant.

If successful in human trials, the latest treatment methods would be direct and effective, rather than relying on roundabout lifestyle changes or expensive, intrusive technology. "SUMO-1 gene therapy may be one of the first treatments that can actually shrink enlarged hearts and significantly improve a damaged heart's life-sustaining function," senior researcher Dr. Roger J. Hajjar, director of the Cardiovascular Research Center at the Icahn School of Medicine of Mount Sinai, said in a statement.

Prior studies have revealed that SERCA2 is also missing in many heart failure patients, suggesting that proper heart function requires well-regulated levels of both genes to ensure calcium gets sufficiently pumped out of the cells. Now Hajjar and his colleagues are investigating how SUMO-1’s absence leads to a reduction in SERCA2. To explore this interaction, the researchers tested SUMO-1 alone, SERCA2 alone, and a combination of the two. The testing models showed high-dose delivery of SUMO-1, and a combination of SUMO-1 and SERCA2, offered great effectiveness at treating heart failure. SERCA2 alone produced weaker heart contractions, less blood flow, and failed to adequately reduce enlarged heart volumes.

"These new study findings support the critical role SUMO-1 plays for SERCA2 function,” Hajjar said, “and underlie the therapeutic potential of SUMO-1 gene replacement therapy for heart failure patients.” Hajjar’s team has moved incredibly fast through the trial phases, he said, as he’s now in the process of securing approval from the U.S. Food and Drug Administration (FDA) to test the novel SUMO-1 gene therapy in heart failure patients. "I think this is a really very unique example of rapid translation of a promising medical therapy from an initial discovery to pre-clinical trials,” Hajjar said.