Abstract
Diabetes increases the prevalence of heart failure by 6–8-fold, independent of other comorbidities such as hypertension and coronary artery disease, a phenomenon termed diabetic cardiomyopathy. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. While fairly effective at delaying disease progression, these treatments do not reverse the cardiac damage associated with diabetes. One potential alternative avenue for targeting diabetes-induced heart failure is the use of adeno-associated viral vector (AAV) gene therapy, which has shown great versatility in a multitude of disease settings. AAV gene therapy has the potential to target specific cells or tissues, has a low host immune response and has the possibility to represent a lifelong cure, not possible with current conventional pharmacotherapies. In this review, we will assess the therapeutic potential of AAV gene therapy as a treatment for diabetic cardiomyopathy.
Highlights
Cardiac apoptosis is a common feature of the diabetic heart and end-stage heart failure in both clinical and preclinical contexts [7]
In a chronic disease such as diabetes, we have shown that administration of rAAV6-caPI3K gene therapy to mice with type-1 diabetes-induced diastolic dysfunction, attenuated cardiac dysfunction and oxidative stress [108]
The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Patients with Cardiac Disease (CUPID) trial was the first human study that investigated the use of Adeno-associated viral vector (AAV) for heart failure by targeting impaired Ca2+ handling utilising sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a)-AAV gene therapy [115]
Summary
Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy – current and future perspectives. Several key signalling pathways have been identified that drive the pathological changes associated with diabetes-induced heart failure. This has led to the development of multiple pharmacological agents that are currently available for clinical use. One potential alternative avenue for targeting diabetes-induced heart failure is the use of adeno-associated viral vector (AAV) gene therapy, which has shown great versatility in a multitude of disease settings. AAV gene therapy has the potential to target specific cells or tissues, has a low host immune response and has the possibility to represent a lifelong cure, not possible with current conventional pharmacotherapies. We will assess the therapeutic potential of AAV gene therapy as a treatment for diabetic cardiomyopathy
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