THERAPEUTIC POTENTIAL OF INTESTINAL PACING FOR OBESITY

DESCRIPTION (provided by applicant): The prevalence of obesity is rising to epidemic proportions around the world at an alarming rate. Obesity is a serious medical problem: in the United States, it is estimated that about 300,000 deaths are caused by obesity every year; more than $100 billion is spent each year for the treatment of obesity and its primary co-morbidities. However, currently there is no satisfactory therapy for morbid obesity and there is a great need to explore new therapeutic options. The long-term aim of this project is to develop a safe and effective therapy using intestinal electrical stimulation for the treatment of morbid obesity. This is based on our preliminary data demonstrating that intestinal electrical stimulation inhibits gastric motility, induces vomiting and reduces food intake. The aim of this project is to prove feasibility of intestinal electrical stimulation for the treatment of obesity in dogs. Specific aims are: 1) to study the effect of intestinal electrical stimulation on gastric tone/contractions as well as gastric emptying and to derive the most effective stimulation method that inhibits gastric motility; 2) to investigate the efficacy and safety of intestinal electrical stimulation in reducing food intake; and 3) to study vagally-mediated mechanisms involved with intestinal electrical stimulation. It is anticipated that intestinal electrical stimulation inhibits gastric contractions or induces gastric relaxation, impairs gastric myoelectrical activity and delays gastric emptying, leading to a significant reduction in food intake in a canine model. It is further hypothesized that the inhibitory effects of intestinal electrical stimulation on gastric motility and food intake are mediated via the vagal afferent pathway. Further studies on the long-term effects of intestinal electrical stimulation on weight loss, possible mechanisms involving certain hormones, such as CCK, and the development of an implantable stimulator will be the topics of the Phase II application.