Inflammatory Response Linked to Glucose Levels

25/07/05 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 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.