CMCC 1639
Novel Obesity Treatment
Inventors: Umut Ozcan, Lale Ozcan
Categories: Therapeutics
SubCategories: Endocrinology, Metabolic Disease
Keywords: Obesity
Invention Description:
Leptin is a hormone that suppresses appetite through its action on hypothalamic neurons. Its discovery over a decade ago generated excitement for a new obesity treatment. However, it was found that obese people are unresponsive to leptin due to the development of leptin resistance in the brain. Dr. Ozcan’s current work shows that in the presence of obesity, the hypothalamus of mice has increased stress in the endoplasmic reticulum, which blocks leptin action in the hypothalamus. During stress, the endoplasmic reticulum cannot function properly to assemble and fold proteins. Dr. Ozcan’s work further shows that using chemical chaperones, low molecular weight compounds that assist in protein folding, can re-sensitize the brain of obese mice to leptin. When obese mice were pretreated with a chemical chaperone, either 4-phenyl butyrate (4-PBA) or taurine-conjugated ursodeoxycholic acid (TUDCA), followed by treatment with leptin, the mice had significant weight loss.
Applications:
With obesity being the second leading cause of preventable premature death in the U.S., the demand for an effective obesity treatment is growing. Dr. Ozcan’s work demonstrates that 4-PBA and TUDCA sensitize the brain to leptin, thereby providing a novel combination treatment for obesity.
Competitive Advantages:
There is no definitive treatment for obesity. Diets and exercise are the basic techniques used to lose the weight. A few weight loss drugs are available, but are associated with medical complications, side effects or safety concerns. As a last option, some obese people are referred for gastric bypass surgery which has several inherent risks. By comparision, both 4-PBA and TUDCA are oral drugs that are safe in humans and FDA approved for clinical use, and the safety profile of leptin shows no systemic toxicities at any dose. Therefore, chemical chaperones when administered with leptin could provide a highly effective appetite suppressing and bodyweight lowering treatment.
Business Opportunity:
Exclusive license, Sponsored research
Key Publications: Cell Metab. 2009 Jan 7;9(1):35-51
IPStatus: Pat. Pend.