Nonviral Gene Therapy Holds Promise for Heart Diseases in the Elderly

Scientists at The Ohio State University Wexner Medical Center are exploring innovative nonviral gene therapy to address age-related heart conditions. Their research indicates that enhancing levels of brown fat or increasing a specific fat molecule released by this energy-burning tissue can help maintain cardiac health.

"Aging often leads to cardiovascular disease, which significantly affects those over 65. We've discovered a link between lower levels of the lipokine 12,13-diHOME and this condition. Increasing this lipokine appears to restore heart function," said Kristin Stanford, Ph.D., professor at The Ohio State University College of Medicine and associate director of the Dorothy M. Davis Heart and Lung Research Institute.

The research, conducted in collaboration between Ohio State's Colleges of Medicine and Engineering, was recently published in Nature Communications, a prestigious scientific journal.

Brown fat is one of two types of fat found in humans and other mammals. Often referred to as "good" fat, it burns energy and generates heat through thermogenesis—unlike ordinary white fat.

In this study, researchers examined blood samples from both young and older human subjects as well as mice. They found that levels of 12,13-diHOME decrease with age for both males and females. Transplanting brown fat from younger to older mice was shown to improve cardiovascular function. Prior research at Ohio State indicated that exercise increases 12,13-diHOME levels, thereby protecting the heart.

Seeking a way to stimulate lipokine release without exercise, researchers employed a nonviral gene therapy called Tissue Nanotransfection (TNT) to elevate 12,13-diHOME in older mice of both genders.

"Using TNT to boost 12,13-diHome levels over six weeks significantly reduced cardiovascular aging effects. The improvements observed in ejection fraction and heart pumping cycles were remarkable," said Daniel Gallego-Perez, Ph.D., a professor and the Edgar C. Hendrickson Chair in Biomedical Engineering at The Ohio State University. Gallego-Perez is also the director of Advanced Nanotherapeutics at the Gene Therapy Institute and the lead inventor of TNT, a patented technology developed at Ohio State.

Scientists also discovered that 12,13-diHOME can directly block CaMKII, a protein crucial for calcium regulation in heart cells. This finding helps explain how 12,13-diHOME may help sustain heart health as it ages.

"With older adults comprising the fastest-growing demographic and facing the highest risk of developing heart disease, innovative technologies like those we're investigating are essential to combat heart disease in later life," Stanford said.