Preventing post-ERCP pancreatitis with a combination of small molecules

Stanford researchers are developing an improved prophylactic against pancreatitis caused by endoscopic retrograde cholangiopancreatography (ERCP), by targeting two key inflammatory pathways. ERCP is a common gastrointestinal procedure that leads to pancreatitis in 3-15% of patients. Post-ERCP pancreatitis can be life-threatening, excruciatingly painful, and costly. Patients and healthcare providers would both benefit from more effective and practical pancreatitis prevention, beyond the current options of indomethacin, stenting, and IV hydration.

The inventors have discovered that calcineurin inhibitors prevent post-ERCP pancreatitis by blocking pressure-induced inflammatory signals. Additionally, a calcineurin inhibitor could be combined with indomethacin to target two distinct inflammatory pathways, achieving higher effectiveness than indomethacin alone. The inventors are formulating this combination for rectal administration to target pancreatic circulation via the portal vein. This method can be smoothly incorporated into ERCP procedures, because rectal indomethacin is the standard-of-care in many facilities.

Stage of Development: Preclinical studies in a mouse model of ERCP showed that calcineurin inhibitors lowered pancreatic inflammation, edema, and tight junction disruption when delivered systemically, intraperitoneally, or via radiocontrast solution.