Glycation End Product Inhibitor Protects Against Diabetic Vascular Complications

The advanced glycation end product inhibitor LR-90 has anti-inflammatory properties that may protect against diabetic vascular complications. Dr. Samuel Rahbar from City of Hope National Medical Center, Duarte, California said that,  "Glycation and inflammation are closely intertwined in the development of diabetic complications."  "LR-90 may be a new class of drug that can target both pathways."

Dr. Rahbar and colleagues evaluated the effects of LR-90 on the expression of various inflammatory mediators associated with monocyte activation and adhesion.

LR-90 inhibited the expression by stimulated monocytes of the receptor of advanced glycation end product and such proinflammatory genes as MCP-1, IP-10, and COX-2, known to be involved in atherosclerosis, the authors report.
LR-90 also inhibited MCP-1 protein expression and suppressed NOX2 activation and oxidant stress in monocytes, the results indicate.  Monocytes treated with LR-90 failed to adhere to endothelial cells when stimulated, the researchers note, but LR-90 had no apparent impact on monocyte cell viability after 24 hours of exposure.

"Our study shows for the first time that the advanced glycation end product inhibitor LR-90 also has anti-inflammatory effects on activated monocytes and thus may have dual beneficial effects in the treatment of inflammatory diseases such as atherosclerosis and other diabetes complications," the investigators write.

"Animal investigations on the effects of LR-90 have been completed in animal models of Type 1 and Type 2 diabetes," Dr. Rahbar said. "The drug has significantly prevented diabetic complications in the kidneys, retina, and aortic walls of those animals."

"We are undertaking collaborative studies to explore effects of the drug on diabetic apo-E knock out mice both in a preventive (after start of diabetes) and therapeutic (after 12 weeks of diabetes)," Dr. Rahbar added. "Via these studies, we will assess whether LR-90 can prevent development of atherosclerosis."
Diabetes 2007;56:647-655.

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