Nerve growth factor: Does this have the potential to become a miraculous treatment for diabetic heart?

Diabetic heart, which includes any condition causing pathological changes in blood vessels, cardiac muscle or valves and cardiac rhythm in diabetic patients, such as diabetic cardiomyopathy and ischemic heart disease, is an important cause of mortality in diabetic patients. However, strategies for the treatment of diabetic heart have not been well documented. Recent, large, clinical trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) and the Veterans Affairs Diabetes Trial (VADT), failed to show glucose lowering effects on mortality in diabetic patients, suggesting the need for safer ways to lower glucose, as well as specific strategies for the treatment of diabetic heart. Diabetic cardiomyopathy is characterized by the presence ofmyocardial damage, a disturbance in the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. A recent study by Meloni et al. evaluated the impact of nerve growth factor (NGF) gene therapy on the prevention of cardiomyopathy in type 1 diabetic mice. They used a gene transfer technique and investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice, using two types of adeno-associated viral vectors (AAV) injected in mice in two different ways – by a direct intramyocardial injection or a systemic delivery by venous injection. Both methods of NGF gene delivery reduced the deterioration of cardiac function and showed additional protective effects on myocardial microvascular rarefaction, interstitial fibrosis, and apoptosis of endothelial cells and cardiomyocytes (Figure 1). The content of NGF in the heart is altered by heart disease. Reduced myocardial expression of NGF is reported in heart failure. Several reports have described that diabetes reduces cardiac NGF expression. Ieda et al. showed that the levels of NGF messenger ribonucleic acid (mRNA) did not change in hearts of 8 weeks’ streptozotocin (STZ) rats, but were significantly downregulated in 16 weeks’ STZ hearts. Meloni et al. also showed reduced NGF mRNA levels in the heart at 12 weeks of diabetes in their study. There is emerging evidence that NGF showed protective effects in heart Diabetic heart