Mercury Therapeutics: Breakthrough For Type-2 Diabetes Patients
Mercury Therapeutics has developed a novel lead generation platform to identify small molecule activators of protein kinases involved in the regulation of energy metabolism. The technology employed is in an interrelated series of in-vitro and cell-based protein kinase and cell metabolism assays that allow for the rapid filtering of the numerous hits that are routinely identified in most types of high throughput screening campaigns, particularly those seeking to develop activators of protein kinases. MTI's specific implementation of this technology is to identify and develop small molecule activators of AMP activated protein kinase (AMPK) to treat type-2 diabetes ("T2DM") and metabolic syndrome utilizes both proprietary technology and in-house improvements in assay development for activators of protein kinases with structures that include multiple subunits like, AMPK.
T2DM is of epidemic proportions in the western hemisphere, having doubled in incidence in the past two decades. According to an article in the New York Times on May 16, 2006, diabetes is the only disease in the U.S. with a death rate that is still rising, accounting for over 225,000 deaths per year. It is estimated that there are at least 20 million diabetics in the USA, with a third still undiagnosed. In addition to the direct morbidity and mortality due to diabetes, elevated fasting blood glucose levels, even levels below the threshold for a diabetes diagnosis, have been associated with a significantly increased risk of heart attack and stroke. The American Diabetes Association has estimated that $92 billion was spent in 2002 on diabetes care. Of that, $20 billion was for the diabetes drug market, accounting for over 12% of total pharmaceutical sales.
Through its proprietary screening platform, MTI has identified multiple small molecule chemotypes that potently activate AMPK directly in vitro as well as in cultured cells. MTI is in the process of applying for patent protection on these novel core structures and simultaneously initiating preclinical studies on these lead series. MTI has also identified a number of small molecules that stimulate AMPK activity indirectly in a variety of mouse, rat and human cell lines. Of these cellular actives, MTI has been able to demonstrate that this activity in cell culture corresponds to an effect in-vivo, inducing the accelerated clearance of elevated blood glucose levels in mouse models. These assays were performed in two ways. In the first model, normal lean mice were challenged with a large dose of glucose and were treated 20 minutes later with an AMPK activator. Mice that were treated with a known AMPK activator or with the MTI compounds showed an accelerated rate of clearance of blood glucose levels within 30 to 90 minutes of treatment, compared to mice who only received glucose.
AMPK plays a key role in maintaining cellular and whole body energy balance. It is found in all cells and tissues, but most importantly in skeletal muscle, liver, and adipose tissue. AMPK activation shifts both intracellular and whole body metabolism away from cholesterol, fatty acid and triglyceride synthesis (fat storage) and toward