Promising new mechanism to treat diabetes
SANTA CLARA, Calif. -- July 22, 2005 – Scientists at Galileo Pharmaceuticals, Inc. have demonstrated a direct relationship between inflammation and glucose levels. Through its recently established metabolic disease program, Galileo confirmed in preclinical models that inhibiting lipoxygenases, known mediators of inflammatory response, significantly lowers blood glucose levels in animal models of diabetes.
"Metabolic disease is a health concern of near-epidemic proportions, particularly in the US," said Lloyd M. Kunimoto, president and chief executive officer of Galileo Pharmaceuticals, Inc. "We are encouraged by our initial study, which confirms the role of inflammation in the regulation of carbohydrate and lipid metabolism, and validates our proprietary drug discovery platform using Conserved Inflammatory Pathway (CIP) modulators to treat a wide variety of important diseases such as asthma, arthritis, diabetes, and other diseases mediated by inflammation."
In a paper presented today at the Therapeutic Approaches to Obesity and Related Disorders conference in Washington DC, Galileo scientists demonstrated that administration of a proprietary dual 5- and 15-lipoxygenase inhibitor reduced resting glucose levels by approximately 20% in the db/db mouse model of diabetes without affecting insulin levels. This compares favorably with the reduction obtained by the administration of rosiglitazone, a widely-prescribed treatment for type 2 diabetes that acts by sensitizing cells to insulin. Additional presentation of these data will be made in October at SMi's 7th Annual Diabetes meeting in London.
"Our goals are to identify novel mechanisms for controlling glucose levels via the regulation of inflammatory processes, and to develop drug candidates that are based on these mechanisms," said David Liebowitz, MD, PhD, chief scientific officer and executive vice president of research and development for Galileo Pharmaceuticals, Inc. "There is increasing scientific evidence that suggests that inflammation is a key component of onset and progression of metabolic disease. We have already identified potent lipoxygenase inhibitors that have shown activity in preclinical animal models of diabetes and are evaluating more potent and pharmacologically optimized leads in appropriate animal models."
Lipoxygenases are enzymes which play a key role in the synthesis of inflammatory mediators called leukotrienes, and trigger the progression of several diseases mediated by inflammation. Two key members of the lipoxygenase pathway, 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) have been indicated in a number of diseases states including asthma, arthritis, atherosclerosis, diabetes, osteoporosis, and cancer. Lipoxygenases are common in plants where they are involved in modulating a number of diverse physiological aspects including signaling, growth and development, pest resistance, and senescence, or response to wounding.
About CIP Modulators Galileo's proprietary drug discovery platform exploits the similarities between the genomes of plants and humans to rapidly identify drug-like compounds, which can then be modified and optimized into small molecule drug compounds. Several pathways regulating inflammation are found in both plants and animals. Examples of target classes within these conserved pathways that are amenable to Galileo's Conserved Inflammatory Pathway (CIP) platform include kinases, lipoxygenases, nuclear receptors, and phosphatases. Galileo has demonstrated that several of the compounds produced by the plants in response to stress to regulate specific pathways also modulate the corresponding human pathway. Galileo uses the stress-induced plant compound libraries as starting points and applies its medicinal chemistry optimization to develop small molecule drug candidates for the treatment of inflammatory and metabolic disease.
About Galileo's Lipoxygenase Program
Galileo is developing several novel, potent and selective 5-LO inhibitors for the treatment of inflammatory disorders and diabetes as well as a dual 5-LO and 15-LO inhibitor for the treatment of osteoporosis and diabetes. These compounds represent first-in-class chemistry and a biological mechanism of action distinct from the 5-LO inhibitors previously evaluated by pharmaceutical companies. Galileo's first 5-LO inhibitor is scheduled to enter clinical trials in 2006 as a potential treatment for asthma.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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