NASH
The Next Big Global Epidemic
NAFLD
~80
Million Americans
NASH
~16
Million Americans
Cirrhosis
~1TO3
Million Americans
NASH is a serious form of nonalcoholic fatty liver disease (often abbreviated as NAFLD) and is the liver manifestation of metabolic syndrome, a constellation of disorders that includes insulin resistance, persistently elevated insulin levels, Type 2 diabetes and obesity. Excessive caloric intake and a sedentary lifestyle can result in a state of overnutrition and drive pathological metabolic processes in the liver that significantly contribute to the onset of NASH. In a state of overnutrition, one of the cell’s important energy sources called pyruvate rapidly enters the mitochondria of cells via the mitochondrial pyruvate carrier (MPC), leading to the modification of multiple downstream pathways and functions in the liver’s cells. The effects of these processes include insulin resistance, further increases in fasting plasma insulin, increased fat storage, decreased fat oxidation, inflammation, cell damage and scarring, or fibrosis. Over time, fibrosis in liver cells may lead to cirrhosis, and ultimately, such diminished liver function may require a liver transplant or lead to liver cancer, and potentially, liver-related death.
NASH is the liver manifestation of metabolic syndrome, a constellation of disorders that includes insulin resistance, Type 2 diabetes and obesity.
There are currently no approved therapies for the treatment of NASH. The prevalence of NASH is growing globally and in the United States alone, an estimated 16 million people have NASH, a number which is projected to increase to 27 million by the year 2030. It is estimated that approximately half of NASH patients also have Type 2 diabetes, and are at greater risk for poor clinical outcomes.
Mechanisms Involved in the
Pathophysiology of NASH
In the setting of overnutrition, an excess of pyruvate, an energy source for cells, is rapidly transported into the mitochondria of cells through the MPC, leading to the modification of multiple downstream pathways including transcription factors. The effects of these modifications include insulin resistance, increased fat storage, decreased fat oxidation, inflammation, cell damage and fibrosis.
Given that overnutrition is a common driver of NASH and Type 2 diabetes, we believe our unique approach, focused on mitigating the negative effects of overnutrition, including insulin resistance, has the potential to provide therapeutic benefits in both NASH and Type 2 diabetes.