AptamiR Therapeutics has created a revolutionary approach to cure human obesity and related cardio-metabolic disorders by converting fat-storing adipocytes into fat-burning adipocytes.
Article in press in Nucleic Acid Therapeutics
Title: Metabolic Benefits of microRNA-22 Inhibition
Diabesity is a growing pandemic with substantial health and financial consequences. We are developing microRNA-based drug candidates that transform fat storing adipocytes into fat burning adipocytes (browning effect) to treat metabolic diseases characterized by lipotoxicity. Through phenotypic screening in primary cultures of human subcutaneous adipocytes, we discovered that inhibition of microRNA-22-3p by several complementary antagomirs resulted in increased lipid oxidation, mitochondrial activity and energy expenditure. These effects may be mediated through activation of target genes like KDM3A, KDM6B, PPARA, PPARGC1B and SIRT1 involved in lipid catabolism, thermogenesis and glucose homeostasis. In the model of Diet-Induced Obesity in mice of various ages, weekly subcutaneous injections of various microRNA-22-3p antagomirs produced a significant fat mass reduction, but no change of appetite nor body temperature. Insulin sensitivity as well as circulating glucose and cholesterol levels were also improved. These original findings suggest that microRNA-22-3p inhibition could become a potent treatment of human obesity and type 2 diabetes mellitus, the so-called diabesity characterized by lipotoxicity and insulin resistance.