beth israel deaconess medical center a harvard medical school teaching hospital

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Dr. Mark Williams

Drugs Inhibiting AGE Formation

Dr. Mark Williams focuses on clinical studies of glycation inhibitors, including the investigational drugs Pimagedine and Pyridorin. These drugs may protect remaining kidney function in patients who have diabetes and kidney disease, and may also be helpful in treating patients with end-stage renal disease on hemodialysis.

High blood sugars from diabetes can cause irreversible complications through a variety of biochemical mechanisms. Excessive interaction of glucose with proteins leads to the formation of substances called advanced glycated end-products, or AGEs. People with diabetes who have chronically elevated blood glucose levels tend to form excessive amounts of AGEs in various parts of the body, resulting in cross-linking between involved proteins.

Increased AGE formation has been observed in a variety of animal tissues, including the glomerular basement membranes of the kidney and the coronary arteries. People with diabetes have been shown to have higher levels of AGEs in their blood than non-diabetics, and these levels rise in patients with diabetic kidney disease as the kidney disease worsens. Researchers hypothesize that AGEs also may be important in the development of coronary artery disease and peripheral vascular disease in people with diabetes.

Dr. Williams also directs clinical research projects involving uremic glucose intolerance, the comparative roles of angiotensin-receptor blocking drugs on diabetic nephropathy, and longitudinal patient/physician education in patients at risk for progressive kidney disease.