Alteon Inc reported that a new preclinical study demonstrates the ability of ALT-711, Alteon's lead A.G.E. Crosslink Breaker, to reduce diabetes-associated cardiac abnormalities, including the progression of collagen deposition and growth factors in the diabetic heart in rats. The study also suggests that Advanced Glycation End-products, or A.G.E.s, play a central role in many of the alterations observed in the diabetic heart.
Diabetic heart disease is associated with coronary heart disease, left ventricular hypertrophy and cardiac fibrosis, all of which contribute to the development of heart failure. Though the clinical features of diabetic heart disease have been identified, its pathogenesis and the mechanisms underlying the abnormalities in the diabetic heart have not been fully identified. A.G.E.s and A.G.E. crosslinks, glucose-protein chemical bonds that have been shown to cause the progressive stiffening of the tissues, vessels and organs throughout the body, are thought to play a role in diabetic heart disease.
The purpose of the study was to investigate the mechanisms underlying diabetic cardiomyopathy and to determine the effects of an A.G.E. Crosslink Breaker, ALT-711, on diabetes-induced heart disease. In a paper based on the study's findings, "A Breaker of Advanced Glycation End Products Attenuates Diabetes-Induced Myocardial Structural Changes," the authors conclude that A.G.E.s play a central role in many of the changes observed in the diabetic heart, and that treatment with ALT-711 leads to the reduction of diabetes-associated cardiac abnormalities in rats.
ALT-711 was evaluated in diabetes-induced cardiac disease by treating a strain of rats whose hearts had a number of characteristics known to lead to damaged heart tissue: increased left ventricular (LV) mass; increased brain natriuretic peptide (BNP) expression; decreased LV collagen solubility; and increased collagen III gene and protein expression of connective tissue growth factors. These diabetic hearts also were shown to have significant increases in A.G.E.s and increased expression of A.G.E. receptors. Treatment with ALT-711 significantly reduced the cardiac accumulation of A.G.E.s and increased collagen solubility to the same level observed in control (normal) animals. Furthermore, ALT-711 completely prevented the increase in collagen III gene and protein expression. The authors postulate that therapy with ALT-711 could prove useful in attenuating cardiac remodeling and in reducing the development of cardiac disease in diabetes.
"This study is consistent with the previous clinical and preclinical testing of ALT-711 published to date," said Kenneth I. Moch, President and CEO, "demonstrating the ability of ALT-711 to have beneficial effects on certain age-related and diabetes-related cardiovascular pathologies."