Development of an oral therapeutic to mimic the anti-diabetic effects of gastric bypass surgery

DESCRIPTIONprovided by applicantGlucose homeostasis and regulation of food intake are both promoted by the secretion of gut hormones following nutrient stimulation of enteroendocrine cellsL cellsin the lower gutThis process is impaired in diabetes but is restored when delivery of dietary compounds such as amino acids and fatty acids to the lower gut is facilitatedThis effect of delivery of nutrients to the lower gut is observed after gastric bypass surgery and during fermentation of carbohydrates in the colonboth of which can result in resolution of diabetesThese approaches to deliver nutrients to the lower gut are not without complicationsalthough their resulting efficacy is often superior to existing drugsCurrently marketed anti diabetes drugs have deficiencies in efficacydurability of effectand safetyand the pharmaceutical industry hasthereforebeen looking for novel approaches to restore impaired gut hormone secretionBioKier has identified a simpledirectsafe method to deliver one of the key nutrients to the colon in a way that can be developed for the treatment of diabetes and other conditions characterized by impaired L cell stimulationBioKierandapos s concept involves the approach of delivering nutrients as gut hormone secretagogues to the colon via a colon targeting formulation for the treatment of diabetes and other disordersAcute studies conducted by BioKier showed that direct delivery via catheter of specific nutrients to the colon of diabetic animals and humans restored the oral glucose induced gut hormone responseChronic treatment with an oral formulation of a representative nutrient completely prevented the development of diabetes in a diabetes prone rat model and supported the concept that the approach could lead to development of a marketable therapeuticBased on lead selection data from the acute clinical studiesL glutamine was formulated in an oralsustained releasecolon targeted capsule for testing in typediabetes patientsIn order to conduct human testingthe glutamine formulation needs to be tested in animals for safetyas is proposed in Phase I of the SBIR application in a local toxicity and toxicokinetic study of BKRcapsules in dogsPhase II involves conduct of a Phaseclinical trial to evaluate pharmacokineticsplasma GLPand insulin biomarker responsesand safety of BKRin diabetes drug na ve typediabetes patientsEndpoints are to assess the bioavailability of L glutamine and measure biomarkers to confirm colonspecific deliveryProgress thus far has attracted the interest of several potential pharmaceutical partners who have indicated the results of the clinical study to be funded by this application are crucial to discussions of a licensing agreement PUBLIC HEALTH RELEVANCEInsulin resistance and typediabetes are major health risks increasing in all parts of the worldBariatric surgeries in which sections of the upper small intestine are bypassedsuch as RYGBare widely documented to resolve diabetes within days in a very high percentage of obese typediabetes patientsWe propose an orally deliverable therapeutic designed to mimic the anti diabetic effects of the intestinal shortening surgery