Promising Drug Candidate Offers Hope for Difficult-to-Treat Heart Failure

Researchers at the University of Arizona's Sarver Heart Center have identified a novel drug candidate that shows potential in reversing a specific type of heart failure, known as heart failure with preserved ejection fraction (HFpEF), in mouse models. HFpEF occurs when the heart muscle becomes stiff, making it difficult for the heart to fill properly, which is a common form of heart failure linked to aging and diabetes.

The study, published in the journal Cell Metabolism, uncovered a key mechanism involving an enzyme that, under pathological conditions, escapes its typical location within cells. This mislocalization triggers a cascade that leads to the production of harmful glucose byproducts, reducing the elasticity of the heart tissue. Senior author Dr. Hossein Ardehali explained that this process is closely related to diabetes, a significant risk factor for HFpEF, as continuous sugar overload causes cellular dysfunction.

By investigating this pathway, the team identified a molecule capable of neutralizing the damaging glucose byproducts. In mouse models, this molecule successfully reversed the signs of heart failure, restoring proper heart function. This breakthrough offers a promising avenue for developing treatments specifically targeting the underlying causes of HFpEF.

To further understand the disease mechanism, the researchers developed the first mouse model of spontaneous HFpEF. They examined endothelial cells lining blood vessels, tracking how these cells transition from healthy to dysfunctional states. This research revealed that enzyme interactions and glucose metabolism within endothelial cells play a crucial role in disease development.

Currently, treatment options for HFpEF are limited, mainly focusing on lifestyle changes and cardiac rehabilitation. Some benefits have been observed with new diabetes medications called SGLT2 inhibitors, but additional therapies are needed. The researchers hope their drug candidate can expand the therapeutic options available for patients with HFpEF.

The next steps involve additional laboratory testing to confirm the drug’s efficacy, followed by plans to evaluate its safety and effectiveness in human trials. Dr. Ardehali expressed optimism, noting that this new treatment approach could significantly reduce the incidence of HFpEF and improve patient outcomes.