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Synvista Therapeutics' Alagebrium Shows Potential for use in Treating Diabetes-Related Gastrointestinal Complications
Date:10/25/2007

tor for AGEs) signaling in an in vivo model of diabetes. He used two drugs aminoguanidine, a well characterized inhibitor of AGE formation, and alagebrium, a novel compound that acts as an AGE-crosslink breaker. The study showed that diabetes resulted in an accumulation of serum AGEs and that there was a 50% reduction in myenteric nNOS expression which was reversible by either aminoguanidine or alagebrium. This is the first reported evidence for the potential importance of AGE signaling in the pathogenesis of enteric neuropathy. In this study, late administration of alagebrium reduced serum AGEs to control levels and also restored nNOS levels. Further studies will be needed to understand the mode of action of alagebrium, however, the results of the study suggest that countering the AGE-RAGE signaling pathway may be a major target for diabetes related gastrointestinal complications, particularly those that arise from reduction of nNOS expression.

"I am quite enthused by the observation that alagebrium may preserve nNOS activity, which would allow it to advance as a leading candidate for clinical development in the fight against this challenging disease," said Dr. Pasricha.

Patients with diabetes commonly experience gastric and intestinal dysfunction, however, the mechanism of how this happens is not well understood. The term diabetic enteropathy is often used to explain the disturbance in bowel function such as chronic diarrhea which occurs in 15% or more diabetics. A role for decreased nNOS expression has been suggested as a possible cause for the diarrhea however how diabetes causes such changes in nNOS expression levels is unknown. Dr. Raj Kumar will continue to work on how glycation of nNOS affects its structure and function.

"Dr. Pasricha's ground breaking work may be the first step in providing treatment for gastrointestinal disorders resulting from diabetes," said Noah Berkowitz, M.D., Ph. D. President and Chief Executive Officer of Synvista.
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SOURCE Synvista Therapeutics, Inc.
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