To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: New Anti-Obesity Approach Acts Independently of Leptin URL: http://www.pslgroup.com/dg/95E6.htm Doctor's Guide June 7, 1996
SAN FRANCISCO, June 7, 1996-- The use of oral neurotransmitter modulating drugs to change daily patterns of the chemical messengers dopamine, serotonin and noradrenaline in the brain may offer new treatments for obesity and other metabolic disorders that are more fundamental than current leptin-based approaches, according to studies presented here at the annual meeting of the American Diabetes Association. Researchers at Ergo Science Corporation (Nasdaq: ERGO) used this new approach to achieve significant reductions in body fat in the leptin-deficient ob/ob mouse, an obese animal model widely publicized by several companies developing genetic approaches to obesity therapy. Ergo Science, a Boston-based biopharmaceutical company, has filed patent applications covering this new approach. In one study, "Dopaminergic D1/D2 Synergism Reverses Obesity and Lipid Disorders in the Leptin-Deficient ob/ob Mouse," by E. Tozzo, et. al., Ergo Science researchers established that stimulation of two dopaminergic receptors produced a significant (between 50 and 60%) reduction in food intake, dramatic weight loss and a decrease in fat stores of 22-32% with no significant decrease in lean body (muscle) mass. This approach also improved glycemic control, reducing glucose 57% and insulin 50%, respectively. These effects were accomplished without the administration of exogenous leptin. In a second study, Ergo researchers found that timed administration of a dopamine agonist and a serotonin agonist reduced body fat 30-75% and body weight gain 40-60%. In this study, lean body mass was increased 5-17% confirming that the two drug regimen was able to reduce weight by selectively reducing body fat. Again, these reductions were accomplished without the administration of leptin. The selective reduction in body fat and preservation of lean body mass has significant implications for the treatment of human obesity as improvement in the lean-to-fat ratio is thought to be closely associated with a reduction in the cardiovascular risk factors resulting from chronic obesity. "Genetically obese rodent models are known to have defects in dopaminergic function expressed in the hypothalamic center of the brain which make them interesting models for studying the effects of changes in neurotransmitter activity (such as those associated with dopamine) on metabolic disorders such as obesity," according to Anthony Cincotta, Ph.D., Ergo Science's Director of Research. "Specific targeting of these defects with drugs that stimulate both the D1 and D2 receptors in the brain enabled Ergo scientists to successfully reverse the mouse's obesity and hyperglycemia, in an animal model totally lacking endogenous leptin." "The findings of our preclincial research team, headed by Dr. Cincotta, which are being presented at the ADA, suggest that Ergo Science is on the threshold of a new approach for the treatment of metabolic disease," noted Warren Huff, President and Chief Executive Officer. "These findings provide a substantial new validation for our core technology which has produced consistent results in age-related, seasonal, and now genetic animal models for obesity and diabetes. Our therapeutic approach has also produced a first generation product that is currently being tested in Phase III clinical studies in obese, Type II diabetics." Ronald H. Abrahams, Ph.D., Executive Vice President and head of clinical development at Ergo added, "The findings by Dr. Cincotta and his team point the way towards a number of novel compounds that we will actively screen for effect in the ob/ob mouse model over the next several moths. We are confident that this screening will produce a lead clinical candidate in 1997." According to a recent statement by the American Diabetes Association, the link between obesity and Type II diabetes is very strong. Of approximately 7.5 million Americans with Type II diabetes, at least 80 percent are estimated to be obese (i.e., having a body weight at least 20 percent above ideal body weight.) The Association has also noted that millions more may be at risk for diabetes because they are overweight or have other risk factors. Additional Papers Presented at ADA Provide Further Validation of Ergo's Scientific Approach Ergo Science also presented additional papers at the ADA meeting which provide further evidence of the role of the hypothalamus and CNS in moderating obesity in several animal models. In one study, "The anti-obesity effects of bromocriptine are associated with reduced monoamine turnover in the ventral medial hypothalamus (VMH)," by Shuquin Luo et. al., Ergo Science Corporation investigators studied the effect of timed systemic administration of bromocriptine on metabolism in obese male Syrian hamsters and, specifically, the role it might have in altering noradrenaline, dopamine and serotonin activity in the VMH. The study found that this timed treatment yielded reductions of glucose, insulin, body fat, and an increase in lean body mass. The metabolic changes were associated with dramatic decreases in the levels of serotonin and norepinephrine metabolites in the VMH. "This research has demonstrated for the first time that timed administration of a dopamine agonist/noradrenergic antagonist (bromocriptine) which induces improvements in body composition and glucose tolerance is strongly associated with decreases in VMH neurotransmitter activities known to cause increased appetite, obesity and hyperglycemia," said Dr. Cincotta. In another paper, "Bromocriptine Reverses Obesity Without Influencing Food Consumption in the Syrian Hamster," by Piotr Seislowski, et. al., researchers examined the possibility that an ergot alkaloid -- dopamine agonist can reverse seasonal obesity in a well- recognized animal model. The Ergo Science team administered systemic bromocriptine to animals for two weeks and found that administration of the dopamine agonist not only reversed the existing obese condition, but also reduced levels of lipogenic enzyme activity in the liver without altering food consumption. Ergo Science is a biopharmaceutical company that is developing novel treatments for metabolic and immune system disorders including Type II diabetes and obesity. The Company's approach is to use carefully timed orally administered neurotransmitter modulating drugs to address abnormalities of the neuroendocrine system. Its pioneering work in diabetes and obesity, including its unique two-drug approach in treating chronic obesity, is protected by more than 40 filed or issued U.S. patents. The Company's lead product, ERGOSET(TM) tablets, is currently in Phase III clinical trials. Results from these clinical trials collectively known as the "TRIAD Study" ("Timed Randomized Intervention in Adult Diabetes") are expected to be available in the second half of this year. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. 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