miRNA Biomarker Diagnosis and Anti-Fibrotic Treatment for Liver Disease

OVERVIEW

Georgetown researchers developed innovative methods for diagnosing liver disease or risk of liver disease by measuring levels of miRNAs that regulate the cholecystokinin B Receptor (CCK-BR) downstream signaling pathway. Also, it provides a method of treating liver disease by administering a therapeutic (anti-fibrotic) agent.

BACKGROUND

There are many types of liver disease, which can be caused by infections, inherited conditions, obesity, or misuse of alcohol, to name a few. Diagnosis of liver disease often involves a liver biopsy, and individuals with cirrhosis may be at increased risk of bleeding or other serious complications from such a biopsy. The Georgetown researchers developed methods to diagnose a liver disease or risk of liver disease and methods to treat liver disease after identifying key miRNAs related to the mechanism of action of proglumide. Previously, Georgetown researchers demonstrated that proglumide exerted anticarcinogenic and antifibrotic effects in the pancreatic tissue and provided evidence for the role of epigenetic regulation in the causation of the effects. This current innovation creates a panel based on miRNAs, which are downregulated by proglumide in the pancreas and promote fibrosis, serving as a potential biomarker panel to evaluate the antifibrotic effect of proglumide in pancreatic cancer or liver disease.

Benefit

• Non-invasive methods for diagnosing and monitoring liver disease
• First report of the implication of the role of miRNAs in the mechanism of action of proglumide
• Proglumide is orally bioavailable and was used in the peptic ulcer human clinical trials at 1200 mg. Over 600 subjects in 15 clinical trials have confirmed the broad safety profile of this compound.

Market Application

• Biomarker assay for the antifibrotic and anticancer effect of proglumide.

Publications

• Provisional application US 63/367,741
• Cholecystokinin Receptor Antagonist Improves Efficacy of Chemotherapy in Murine Models of Pancreatic Cancer by Altering the Tumor Microenvironment. Cancers (Basel). 2021 Sep 30;13(19):4949. doi: 10.3390/cancers13194949.
• Targeting the Cholecystokinin Receptor: A Novel Approach for Treatment and Prevention of Hepatocellular Cancer. Cancer Prev Res (Phila). 2021 Jan;14(1):17-30. doi: 10.1158/1940-6207.