Drug Repurposing to Inhibit Oncostatin M in Crohn's Disease.

Area of Science:

• Gastroenterology
• Pharmacology
• Genomics

Background:

• Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with limited treatment options.
• New therapeutic targets and drugs are urgently needed for effective CD management.
• Transcriptomic analysis reveals key molecular differences in intestinal tissues of CD patients.

Purpose of the Study:

• To identify novel drug targets for Crohn's disease using transcriptomics.
• To investigate the role of oncostatin M (OSM) in intestinal inflammation in CD.
• To discover potential drug candidates for CD through a drug-repurposing strategy.

Main Methods:

• Comparative transcriptomics of ileum and colon biopsies from CD patients and healthy controls.
• Immunohistochemistry to confirm OSM expression in patient biopsies and IBD model mice.
• In silico drug screening (PyRx, AutoDock) of FDA-approved drugs against OSM.
• In vitro validation of ecamsule's binding affinity (microscale thermophoresis) and inhibitory effect on inflammatory markers (qRT-PCR).

Main Results:

• Six genes, including OSM, were consistently overexpressed in both ileum and colon of CD patients.
• Strong OSM expression was confirmed in CD patient biopsies and IBD model mice.
• Virtual screening identified 13 candidate compounds, with ecamsule showing significant binding affinity to OSM.
• Ecamsule demonstrated effective binding to OSM in vitro and inhibited downstream inflammatory gene expression (IL6, TNFA, CXCL11).

Conclusions:

• Oncostatin M is a promising therapeutic target for Crohn's disease.
• Ecamsule emerges as a potential drug candidate for CD treatment via repurposing.
• This study highlights the combined power of transcriptomics and drug repurposing for IBD therapy development.