Familial dysautonomia (FD) [MIM#2239001), also known as Riley Day syndrome or Hereditary Sensory and Autonomic Neuropathy III (HSAN-III) is characterized by widespread sensory and variable autonomic dysfunction associated with progressive degeneration of the sensory and autonomic nerves. In FD mice neuronal mitochondria have abnormal membrane potentials, produce elevated levels of reactive oxygen species, are fragmented, and do not aggregate normally at axonal branch points. Our lead compound improved mitochondrial function, protected neurons from dying in vitro and in vivo, and promoted cardiac innervations in vivo. Given that impairment of mitochondrial function is a common pathological component of neurodegenerative diseases, our findings identify a therapeutic approach that may have efficacy in multiple degenerative conditions.

Non-alcoholic steatohepatitis (NASH) induced hepatocellular carcinoma (HCC): Due to increasing rates of obesity and diabetes NASH, a chronic inflammatory liver disease, is affecting millions of patients world-wide and has replaced hepatitis C as the number one reason for liver transplantation in the United States. NASH is associated with hepatocellular ballooning and inflammation, in addition to hepatic steatosis. About 20% of people with NASH will go on to develop scarring (fibrosis) of the liver, which may become severe enough to affect the liver’s function, conferring an increased risk of liver cirrhosis or liver cancer, one of the most fatal cancers worldwide. Our lead candidate, an anti-inflammatory, anti-fibrotic and metabolic compound significantly reduces the incidence of NASH-induced hepatocarcinoma in vivo.

Improving fertilisation rates of couples undergoing IVF treatment: Fertility decreases with age and obesity. Mitochondrial dysfunction is emerging as a key defect that occurs in gametes with obesity and aging. Preclinical studies demonstrated significant improvement of fertilisation rates, sperm motility, gamete quality and embryo development when old and/or obese mice were treated with our lead compound.