Antipodean Pharmaceuticals, Inc. intends to study MitoQ^® for treatment of hepatic inflammatory disorders caused by oxidative stress such as nonalcoholic steatohepatitis (NASH). 

NASH is a manifestation of nonalcoholic fatty liver disease, a disorder that resembles alcoholic liver injury but occurs in the absence of excess alcohol intake.  The histologic manifestations of NASH include lobular inflammation and perisinusoidal fibrosis.  Over time, fibrosis can progress to cirrhosis.

The predominant risk factors for NASH appear to be the combination of insulin resistance and oxidative stress.  Increased levels of free fatty acids in the liver lead to lipid peroxidation and the production of high levels of reactive oxygen species (ROS).  In the absence of adequate antioxidant activity, the accumulation of ROS leads to upregulation of inflammatory cytokines, increased collagen deposition and mitochondrial dysfunction.

Preclinical and clinical studies suggest that mitoquinone may be useful treating the oxidative stress injury in NASH.  In a DDC (diethoxycarbonyl-1, 4,-dihydrocollideine) model of steatohepatitis in rats, treatment with mitoquinone prevented steatohepatitis and Mallory body formation. 

Additionally, in a Phase II clinical study, treatment with MitoQ decreased elevated alanine aminotransferase levels (ALT) in patients with chronic hepatitis C infection (HCV).  This study was initiated in New Zealand in February 2007. The Principal Investigator for the study was Dr Edward Gane, Associate Professor of Medicine, Auckland Hospital.