Intervention on the A.G.E. Pathway

The accumulation of A.G.E.s in tissues leads to inherent changes in matrix deposition, stiffening of tissues, and enhancement of inflammation, all of which contribute to disease pathology. The use of compounds which inhibit the glycation process or break existing crosslinks has emerged as potential therapeutic strategy for cardiovascular and diabetes-related complications. Since the distribution of A.G.E.s is diverse, one could expect a potential benefit in diastolic heart failure, nephropathy and retinopathy. The potential to reverse several disease hallmarks in a variety of tissues indicates that alagebrium may have broad clinical utility for a variety of disease indications.

Clinical Studies of Advanced Glycation End Product Inhibitors and Diabetic Kidney Disease
Author: Williams
Source: Current Diabetes Reports 2004, 4:441–446

The Enzymatic Defence Against Glycation in Health, Disease and Therapeutics: A Symposium to Examine the Concept
Author: Thornalley
Source: Biochemical Society Transactions, 2003, Vol 31, Part 6

Blockade of Receptor for Advanced Glycation End-Products Restores Effective Wound Healing in Diabetic Mice
Author: Goova, et al.
Source: American Journal of Pathology, Vol. 159, No. 2, August 2001

ALT-711 Decreases Cardiovascular Stiffness and Has Potential in Diabetes, Hypertension and Heart Failure
Author: Doggrell
Source: Expert Opinion on Investigational Drugs, 2001

Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker
Author: Kass, et al.
Source: Circulation, 2001, 104:1464-1470