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 steatosis2. 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/WO2023092134A1Related Publication(s)
Kocas-Kilicarslan, Z. N., Cetin, Z., Faccioli, L. A. P., Motomura, T., Amirneni, S., Diaz-Aragon, R., Florentino, R. M., Sun, Y., Pla-Palacin, I., Xia, M., Miedel, M. T., Kurihara, T., Hu, Z., Ostrowska, A., Wang, Z., Constantine, R., Li, A., Taylor, D. L., Behari, J., … Tafaleng, E. N. (2024). Polymorphisms Associated With Metabolic Dysfunction-Associated Steatotic Liver Disease Influence the Progression of End-Stage Liver Disease. Gastro Hep Advances, 3(1), 67–77. https://doi.org/10.1016/j.gastha.2023.09.011
Faccioli, L. A. P., Cetin, Z., Kocas-Kilicarslan, Z. N., Ortiz, K., Sun, Y., Hu, Z., Kurihara, T., Tafaleng, E. N., Florentino, R. M., Wang, Z., Xia, M., Miedel, M. T., Taylor, D. L., Behari, J., Ostrowska, A., Constantine, R., Li, A., & Soto-Gutierrez, A. (2023). Evaluation of Human Hepatocyte Drug Metabolism Carrying High-Risk or Protection-Associated Liver Disease Genetic Variants. International Journal of Molecular Sciences, 24(17), 13406. https://doi.org/10.3390/ijms241713406