Innovative Gene Therapy Shows Promise in Reversing Diabetic Heart Disease in Mice and Human Cardiac Tissues

Recent research has demonstrated that a targeted gene therapy approach could potentially reverse diabetic heart failure, as shown in studies involving mice and engineered human heart tissues. Scientists focused on addressing the metabolic dysfunction in diabetic hearts, where the organ's ability to relax properly between beats diminishes, leading to a condition known as diastolic dysfunction.

The team, comprising researchers from New Zealand, Australia, and other countries, uncovered that diabetic hearts lack sufficient levels of a crucial protein necessary for glycogen breakdown—a process vital for energy production. This protein is part of a cellular pathway called glycophagy, which is disrupted in diabetes, resulting in glycogen accumulation and impaired heart function.

Using a modified virus as a vector, the researchers successfully delivered genes to increase levels of GABARAPL1, a key protein involved in glycophagy. This intervention restored the breakdown of glycogen, reduced its buildup, and improved heart relaxation without altering blood sugar levels or overall body weight in diabetic mice. The treatment notably improved cardiac function and presented a novel approach to addressing the underlying metabolic issues in diabetic cardiomyopathy.

In addition to animal models, the therapy was tested on miniature human hearts derived from stem cells. The treatment enhanced their ability to relax during each heartbeat, a critical indicator of healthy heart function. These findings suggest the potential for future clinical applications that directly target the cardiac issues associated with diabetes, rather than merely managing symptoms.

Moreover, preliminary data indicates that sex differences might influence treatment efficacy, with female hearts showing a stronger response, possibly due to more robust glycophagy activity.

Overall, this research offers promising evidence that gene therapy targeting energy recycling pathways could revolutionize treatment strategies for diabetic heart disease, emphasizing the importance of metabolic health in cardiovascular therapy.

Source: https://medicalxpress.com/news/2025-10-gene-therapy-diabetic-heart-disease.html