Compounds and Methods to Decrease Obesity-related Hepatic Fat Accumulation and Serum Glucose

Technology Description

• Researchers at Johns Hopkins have identified that valproic acid (VPA) and its metabolites may be useful for the treatment of obesity and related metabolic diseases (e.g., type 2 diabetes, fatty liver disease).
• VPA and its cytochrome P450- and beta-oxidation-dependent metabolites activate AMP-activated protein kinase (AMPK), which is a central metabolic regulator.
• 14-day VPA administration in mouse models of obesity decreases liver mass, hepatic fat accumulation, and serum glucose.
• In vitro VPA-treatment of human hepatocytes leads to significant increase in activated AMPK.

Unmet Need

• Metabolic diseases, including type 2 diabetes and obesity, are associated with increased risk of disability, cancer, and premature death (1). In the US, ~35% of adults have cardiometabolic risk factors (2), and ~42% of the population is obese (3).
• Current medications used to treat metabolic disease and obesity have limited efficacy and are associated with unwanted side effects. 
• Therefore, there is a strong need to identify safe and effective therapies to improve health outcomes for patients with obesity and obesity-associated diseases.

Value Proposition

• Potential drug therapy for the treatment of obesity and related metabolic disorders.
• Valproate products are already FDA-approved for other indications (e.g., epilepsy), providing a precedent for human safety.

Stage of Development

• Preclinical studies in mouse models of obesity and in vitro human hepatocytes.

Data Availability

• Data can be found at the following link: https://molpharm.aspetjournals.org/content/85/1/1

Publication

• Valproic Acid is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice (Mol Pharmacol. 2014 Jan;85(1):1-10. doi: 10.1124/mol.113.089755. Epub 2013 Oct 8.).