Elixir Pharmaceuticals Presents New Data on Ghrelin Inhibition at Keystone Meeting
Ghrelin is a naturally occurring hormone secreted by the stomach, which acts primarily at the level of the hypothalamus in the brain. A key metabolic regulator, ghrelin has been shown to stimulate appetite and food consumption, as well as playing a central role in metabolism and energy storage.
According to the Keystone presentation, titled Improved Insulin Sensitivity in Ghrelin Receptor Knockout Mice Assessed by Glycemic Clamp Analyses, ghrelin receptor knockout mice on a high fat diet demonstrated improved insulin sensitivity compared to wild type mice, as measured using the hyperinsulinemic euglycemic clamp and a newly developed hyperglycemic clamp.
"The findings show that ghrelin receptor knockout mice require less insulin to establish glucose homeostasis, and importantly, their pancreatic beta-cell function remains intact. This implies that loss or blockade of ghrelin signaling prevents the development of insulin resistance in high fat diet-induced obesity largely by enhancing insulin-mediated glucose disposal," stated Peter DiStefano, Ph.D., Chief Scientific Officer.
In a second part of the study, mice fed a high-fat diet received a small-molecule ghrelin receptor antagonist. The findings demonstrated that compound-treated mice also showed improved insulin sensitivity, relative to vehicle controls, as measured by the hyperglycemic clamp. Thus, the effect of the antagonist recapitulates the receptor knockout phenotype.
Dr. DiStefano continued, "These preclinical data provide further confirmation of ghrelin's role in metabolic regulation, and we believe that ghrelin receptor antagonism represents one of the most compelling new approaches to treat diabetes and obesity."
Amongst metabolic diseases, diabetes and obesity are at epidemic proportions in the U.S. and represent an enormous unmet medical need. According to the International Diabetes Federation, Type 2 diabetes affects 195 million people worldwide and the number of sufferers could top 330 million by 2025.
Elixir has filed multiple patents on its ghrelin antagonists, with claims that include composition of matter across several different chemical classes, as well as uses of these compounds in a variety of diseases of aging, including metabolic disease.
About Elixir Pharmaceuticals
Elixir Pharmaceuticals is a pharmaceutical company focused on the discovery, development and commercialization of novel pharmaceuticals for the treatment of metabolic diseases such as diabetes and obesity. The Company's scientific founders identified that interactions between specific genes and enzymes can slow the aging process, and are developing compounds that stimulate these interactions and will be used to treat a range of diseases of aging, including metabolic disease. Elixir's product pipeline includes a number of products which the Company believes will have significant advantages over existing products and will address unmet medical needs of the large metabolic disease markets. These include Elixir's phase III products, Glinsuna (mitiglinide) and Metgluna (mitiglinide plus metformin) for the treatment of Type 2 diabetes, and an oral ghrelin antagonist, a compound which blocks the receptor for the hormone, ghrelin, which represents a potential next-generation treatment for a number of metabolic diseases. In addition, Elixir has built upon its knowledge of ghrelin, to advance an oral ghrelin agonist, a compound which stimulates the receptor for ghrelin. Further, the Company's sirtuin products are exemplary of how Elixir continues to use its understanding of the pathways which slow the aging process to identify interesting targets for the development of drugs to treat metabolic disease.
William Heiden, 617-995-7000
Burns McClellan for Elixir Pharmaceuticals
Justin Jackson, 212-213-0006
Juliane Snowden, 212-213-0006
Nicki Kahner, 212-213-0006
Posted: February 2008