Description of the Invention
Obesity and non-alcoholic fatty liver disease (NAFLD) are highly prevalent non-communicable diseases impacting over 30% of adults in Canada and globally. These 2 diseases are important as they are primary risk factors for developing many other chronic diseases including type 2 diabetes (T2D), cardiovascular disease, chronic kidney disease and many cancers. One emerging pathway for treating obesity and NAFLD is brown adipose tissue (BAT). Brown adipose tissue (BAT) is a highly metabolically active organ that is present in adult humans and can be switched on by cold. Metabolic activity of BAT is capable of using 200-300 calories/day. Increasing BAT and subsequently energy expenditure is a unique mechanism of action compared to existing therapies.
Our group demonstrated that targeting the peripheral serotonin signaling pathway can increase BAT activity and affect obesity, insulin resistance and NAFLD in mouse models. HTR2A is the primary serotonin receptor in human BAT with the goal to target this receptor specifically and not other subtypes and those in the central nervous system. Have proof-of-concept data showing in vivo inhibition by a peripherally restrained HTR2A antagonist enhances BAT activity and thermogenesis. Currently developing a med-chem program to synthesize new peripherally restrained HTR2A antagonists.
US 9,937,173 has been granted which protects the use of TPH1 Antagonist for the above purpose.
BAT, Obesity, NAFLD, peripheral serotonin