Network proximity analysis as a theoretical model for identifying potential novel therapies in primary sclerosing cholangitis

TL;DR

This paper proposes a new method to find existing drugs that might work for PSC, a liver disease with no current treatments, by analyzing genetic data.

Contribution

The novel use of Network Proximity Analysis to repurpose licensed drugs for PSC based on genetic associations.

Findings

Over 2000 agents were identified as linked to PSC-related genes using NPA.

Promising candidates include metronidazole and biological agents like basiliximab and abatacept.

Abstract

Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic liver disease with no licensed therapies. Previous Genome Wide Association Studies (GWAS) have identified genes that correlate significantly with PSC, and these were identified by systematic review. Here we use novel Network Proximity Analysis (NPA) methods to identify already licensed candidate drugs that may have an effect on the genetically coded aspects of PSC pathophysiology.

Over 2000 agents were identified as significantly linked to genes implicated in PSC by this method. The most significant results include previously researched agents such as metronidazole, as well as biological agents such as basiliximab, abatacept and belatacept. This in silico analysis could potentially serve as a basis for developing novel clinical trials in this rare disease.

The online version contains supplementary material available at 10.1186/s12920-024-01927-2.

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