Novel Therapy to Prevent Liver Disease

University of Pittsburgh, Kyushu University, and University of Michigan researchers have identified a key pathway involved in the development of cirrhosis with targets to prevent liver disease, thereby reducing the need for liver transplantation.

Description

Previous work has demonstrated a link between a variant on the PNPLA3 gene, rs738409:G, a gene found in 30–50% of the global population, hepatic steatosis, and accumulation of triglycerides in hepatocytes. Novel work has now discovered that lipid peroxidation of polyunsaturated fatty acids (PUFAs) and ferroptosis, a form of iron-dependent cell death are key drivers in the development of liver cirrhosis in carriers of this variant. Targeting the ferroptosis pathway could be a novel approach to preventing liver cirrhosis in carriers of the rs738409:G variant on PNPLA3.

Applications

1. Hepatic steatosis
2. Nonalcoholic steatohepatitis (NASH)
3. Alcoholic and non-alcoholic cirrhosis
4. Hepatocellular carcinoma

Advantages

This novel approach exploits the recently discovered role of ferroptosis in the development of liver cirrhosis in people with the rs738409:G variant on PNPLA3. Through identification of compounds capable of inhibiting ferroptosis, this approach could provide a non-invasive treatment strategy for cirrhosis, including a reduced need for liver transplantation.

Invention Readiness

The role of ferroptosis in the development of cirrhosis in people with the rs738409:G variant on the gene PNPLA3 has been identified. Inhibition of ferroptosis has been shown to improve survival in vitro.

IP Status

https://patents.google.com/patent/WO2023092134A1