The Science

Mechanism of Action



        

A steady flow of new scientific evidence continues to show that patients affected by complex metabolic diseases metabolize fat very differently from healthy people. We are responding to the need for novel solutions by advancing multiple compounds tailored to the unique needs of each metabolic condition we aim to treat.

Once a person becomes obese, the body undergoes certain metabolic changes and becomes “programmed” to create and store more fat, making it much more difficult to reduce body weight. The metabolic adaptations that take place in people with obesity impair the normal release and breakdown of fatty acids from adipose tissue. 

Simultaneously, the body becomes much more efficient in diverting calories from food and storing them as fat.  

This means that in the setting of obesity, high circulating insulin concentrations and levels of fats and sugars lead to stress in the liver and adipose tissue. This cellular stress is propagated by stress and growth signaling molecules such as extracellular regulated kinase (ERK).  Activation of stress pathways leads to changes in fat and cholesterol metabolism, and to the stimulation of the body’s inflammation cascades.  Together these stress pathways lead to the overproduction of fat and glucose by the liver and reduce the availability of fat stored in adipose tissue. The result is that the body locks away calories that otherwise could be used productively as an energy source, and blood glucose levels are harder to control. 

Our lead program in type 2 diabetes, ZGN-1061, and our new molecule, ZGN-1258 for rare disorders including Prader-Willi syndrome, are designed to reduce the activity of these stress mediators, restoring balance to fat metabolism and reducing inflammation.