Modified Kisspeptin Receptor Agonist as Novel Treatment of Non-Fatty Liver Disorder and Non-Alcoholic Steatohepatitis

TAK-448 protected insulin resistant, obese mice against the development of hepatic steatosis:

H& E showing fatty liver.


Invention Summary:

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide that can progress to steatohepatitis (NASH), the leading reason for liver transplants. In the U.S., there are nearly 100 million affected by the disease, which includes children and adults. Since there is no FDA approved drug for NAFLD or NASH treatment, there is an urgent need to develop a novel and effective therapy.

Kisspeptins are peptides that circulate in the blood and bind KISS1R receptors. Scientists from the Rutgers University discovered that increasing KISS1R signaling by administration of the kisspeptin analog (TAK-488) in obese wild type insulin-resistant mice improves insulin resistance, protects against excess fat build-up in the liver (known as fatty liver or steatosis), lowers liver and serum triglycerides, and lowers serum free fatty acids. Moreover, livers from TAK-448 treated mice displayed lower levels of markers for inflammation and fibrosis. By contrast, loss of KISS1R in obese, insulin-resistant mice exacerbated steatosis, insulin-resistance, and metabolic profile.


Market Applications:

  • Novel therapy for the treatment and prevention of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)

Advantages:

  • First pharmacological compound for the treatment of NAFLD
  • Long-lasting analog of kisspeptin-10, a naturally occurring peptide found in the blood
  • Reduces hepatic lipids and inflammatory and fibrosis markers
  • Reduces peripheral fat and lowers blood triglycerides and free fatty acids
  • Protects against insulin resistance

Intellectual Property & Development Status:

PCT application filed. Exclusively licensed and thus not available for licensing and/or research collaboration.

Patent Information:
Licensing Manager:
Bidisha Banerjee
Rutgers, The State University of New Jersey
bb947@research.rutgers.edu
Business Development:
Eusebio Pires
Senior Manager, Technology Marketing & Business Development
Rutgers, The State University of New Jersey
ep620@research.rutgers.edu
Keywords:
Diabetes & Metabolic Disorders
Peptides