Applications

• Therapeutic use of Glial Cell Line-Derived Neurotrophic Factor (GDNF) to treat obesity.
• Potential drug target for further therapeutic development.

Key Benefits

• Growth Factor expression in the brain causes a reduction in high fat diet-induced obesity.
• Fat level reduction has been shown in both mouse and human cells.
• Reducing obesity can lower risk of coronary heart disease and type-II diabetes.

Technical Summary

Obesity is a growing problem, both in the United States and internationally. The US has the highest rate of obesity in the world, with over 30% of adults considered obese, and obesity-related deaths accounting for more than 300,000 American deaths each year. Along with the rise in obesity has come a huge rise in healthcare costs, as well as cases of coronary heart disease, hypertension, and type II diabetes. While awareness of obesity is widespread, treatments focused on lifestyle changes have had little impact. Therefore, there is a large unmet need for drugs or methods that prevent or inhibit obesity.

Researchers at Emory University have discovered that a protein growth factor normally associated with the brain, GDNF, plays a role in both weight management and insulin resistance. Dr. Srinivasan compared transgenic mice over expressing GDNF (GDNF-TG) and fed a regular diet or a high fat diet, to control mice fed the same diets for body weight, insulin resistance, and fat content. GDNF-TG mice were found to resist high fat diet-induced weight gain and display lower insulin resistance. Additionally, they had reduced body fat and lower levels of lipogenesis. These findings are likely due in part to increased metabolism, as GDNF-TG mice have a higher energy expenditure and increased expression of genes involved in fatty acid oxidation than control mice. Further work has shown that GDNF inhibits development of fat cells in human tissue as well, indicating that GDNF itself or compounds targeting GDNF's receptor could serve as effective treatments for obesity and/or metabolic syndrome.

Developmental Stage

• Preliminary work with a transgenic mouse that expresses GDNF has been completed
• Exogenous administration of the compound in wild-type mice significantly alters markers for fatty acid and lipid production
• Additional proof of principle work is ongoing.