A 200-patient phase 2 clinical pilot study will be initiated this month to test the efficacy and safety of a new use, and method of administering, an enzyme inhibitor for critically ill patients developed by UC San Diego bioengineering Professor Geert Schmid-Schönbein.

The study involves a San Diego startup.

According to a UCSD statement, this new use of the FDA-approved drug is based on decades of research by Schmid-Schönbein on the microvascular and cellular reactions that lead to multi-organ failure after a patient has gone into shock. Shock is the second-leading cause of in-hospital deaths in the United States.

Schmid-Schönbein and his colleagues at the UC San Diego Jacobs School of Engineering discovered that under conditions of shock, the epithelial cell barrier that lines the small intestine becomes permeable causing potent digestive enzymes to be carried into the bloodstream and lymphatic system where they digest and destroy healthy tissue, a process he named “autodigestion.” The treatment involves blockading the enzymes with an enzyme inhibitor.

In 2005, the team’s protocol was licensed to San Diego startup InflammaGen Therapeutics under an agreement developed by UC San Diego’s technology transfer office. InflammaGen Therapeutics, a development-stage, critical care company, developed the InflammaGen Shok-Pak, a drug/delivery platform that delivers the enzyme inhibitor through a nasogastric tube directly into the stomach and lumen of the intestine, preventing shock and multi-organ failure. Schmid-Schönbein serves as a scientific advisor to InflammaGen but is not an employee of the company. Instead, he has chosen to focus on continuing to conduct fundamental research on autodigestion at UC San Diego.

“We are testing for the first time whether it is possible to help severely ill patients by blocking autodigestion, a condition in which digestive enzymes not only break down food inside the intestine but also the intestine itself,” Schmid-Schönbein said. “We have pre-clinical results that this treatment can save lives.”

To date, InflammaGen Shok-Pak has been used successfully outside the United States as a rescue therapy in 15 patients, most of whom were diagnosed with life-threatening conditions. In addition, preclinical studies of the technology in two animal species have demonstrated significant increases in long-term survival.