Georgia State scientist receives $25,000 grant to develop mechanisms for treating obesity

Chong Hyun Shin, a research associate professor in the Institute for Biomedical Sciences at Georgia State University, has received a $25,000 grant to develop mechanisms for treating obesity and obesity-related metabolic dysfunctions.

The grant, from the Georgia Research Alliance, aims to identify novel, compositionally distinct therapeutic candidates that are suitable for strong clinical translation.

Globally, obesity is the major driver of metabolic syndrome, which increases the risk of multiple diseases, including Type 2 diabetes. Obesity is linked to 30 to 53 percent of new diabetes cases in the United States. Despite the extensive list of available Type 2 diabetes drugs, only drugs using the incretin axis (e.g. GLP-1 analogs), by modulating satiety and food intake, achieve substantial weight loss and glucose reduction.

However, suppressing hunger by directly modulating neuronal activity in several brain regions leads to multiple concerns, such as rapid weight regain when treatment stops and substantial loss of lean mass. In addition, currently available GLP-1 drugs demonstrate fatal side effects, including pancreatitis and gastroparesis or obstruction. Energy expenditure and fat oxidation, rather than appetite control, are considered key determining factors of weight loss to enhance glycemic control. But many of the drugs stimulating energy expenditure have failed in clinical development or have been withdrawn from the market due to lack of efficacy or side effects.

Shin's team, in collaboration with researchers at Georgia Tech's School of Chemistry & Biochemistry, has developed and identified a novel, orally active small molecule that produced substantial weight loss without affecting food intake or relative lean mass in obese mice. They plan to determine the pharmacokinetic profiles of this molecule by measuring its solubility and metabolic stability outside the body. They will also define the standard pharmacokinetic parameters and tissue distribution of this small molecule in the body.

The dosing regimen that affords the best drug delivery profile will be selected for subsequent studies in overtly obese and diabetic mice. This information, which will be combined with the mechanistic and pharmacokinetic profiling of the newly synthesized analogs, will enable us to engineer one or more small molecule leads with improved potency, selectivity, pharmacokinetics and/or pharmacodynamics."

Chong Hyun Shin, research associate professor, Institute for Biomedical Sciences, Georgia State University

"The proposed project will empower us to determine the therapeutic potential of a unique orally active small molecule yielding improved metabolic outcomes with negligible impact on appetite and lean mass," Shin added. "Our project will further identify a drug prototype, which elicits strong energy expending and anti-hyperglycemic effect as well as lean mass maintaining capacity, for metabolically healthy weight reduction accompanied by diabetes remission."