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Non-alcoholic steatohepatitis (NASH)

Non-alcoholic
steatohepatitis (NASH)

Loomba and Shulman, 2021
Loomba and Shulman, 2021
  • NASH, an advanced form of non-alcoholic fatty liver disease (NAFLD), can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC)

  • Genetic factors, environmental factors, and microbiome alterations are mainly involved in disease progression

Loomba and Shulman, 2021
Loomba and Shulman, 2021
  • Experts estimated that 24% of U.S. adults have NAFLD and more than 6.5% of them have NASH (NIH report, 2021). 20~30% of patients with NASH progress to liver fibrosis in 7 years, and 20% of them progress to cirrhosis in two years.

  • However, since no drugs for NASH are commercially available, off-label drug use is the only available treatment option.

Mechanism of action of GM-X

Mechanism of
action of GM-X

Choi and Kim, 2018
Choi and Kim, 2018
  • In a mouse model, high-fat diet (HFD) feeding increased both serotonin (5-hydroxytryptamine, 5-HT) levels in the portal blood and serotonin receptor 2a (5-HT receptor 2a, Htr2a) expression in the cell membranes of hepatocytes

  • Inhibition of gut-derived serotonin synthesis or direct blocking of the 5-HT2a recepto ameliorates hepatic steatosis by suppressing liver Htr2a signaling.

  • 5-HT is also involved in inflammation and fibrosis-related gene expression in the liver and more importantly, the activation of hepatic stellate cells which is directly connected to the progression of liver fibrosis.

  • The Synthesis of an Htr2a antagonist can provide a potent drug candidate for NASH and liver fibrosis

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