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Elixir Pharmaceuticals Presents Additional Preclinical Data,Demonstrating the Potential of Ghrelin Antagonism to Regulate,Metabolism, Body Weight and Glycemic Control

ociated with a high-fat diet. The presentations further showed that treatment of wild type diabetic and obese mice with a small molecule ghrelin antagonist recapitulated the effects seen in the knockout mice.

In a first series of experiments, Elixir scientists examined the impact of a high-fat diet on fuel utilization and metabolic flexibility in GhrR knockout mice. Increased metabolic flexibility is associated with increased insulin sensitivity and a resistance to diabetes. As expected, long-term exposure to a high-fat diet caused an overall decrease in metabolic flexibility in the wild type mice; however, this trend was reversed in the GhrR knockout mice fed the same diet.

In another series of experiments, GhrR knockout mice were fed a high-fat diet for 15 weeks, with their body weight and food intake monitored throughout the experiment. The results showed after 15 weeks on the diet, the GhrR knockout mice gained 10 percent less weight than the wild type control mice. Additionally, the knockout mice had lower blood glucose, insulin and HbA1c levels. These results indicate the knockout mice are less prone to the development of diabetes.

The scientists then compared the results of the GhrR knockout mice to those obtained with mice treated twice a day for up to 56 days with one of the Company's potent, small molecule GhrR antagonists. As with the GhrR knockout mice, the antagonist-treated mice showed improved glucose and insulin control compared to the mice treated with vehicle. In addition, the GhrR antagonist treatment resulted in a significant reduction in liver fat content with no evidence of liver toxicity relative to the mice vehicle-treated mice.

"Ghrelin antagonism represents one of the most intriguing new targets for addressing metabolic disorders such as Type 2 diabetes, obesity and other metabolic disorders. Our compilation of preclinical data, including these presentations, has shown it is possible to improve glucose control, d
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