Identification of Novel Pepsin Inhibitors to Treat Laryngopharyngeal Reflux Disease

Laryngopharyngeal Reflux Disease (LPRD), an extension of gastroesophageal reflux disease (GERD) occurs when gastric contents are refluxed past the esophagus into the larynx, pharynx, and even the middle ear. Current acid suppression therapy with proton pump inhibitors (PPIs) has proven ineffective because unlike GERD, pepsin is the mechanism behind damaging healthy tissues, not stomach acid. When pepsin is refluxed extraesophageally it can actively digest healthy tissues, damaging cells, leading to mutations and causing subsequent cancers. The objective of this research is to identify new pepsin inhibitors to completely and irreversibly inhibit pepsin’s activity when present in these tissues. Previous work in the project included development of multiple fluorescence assays, which use labeled pepstatin, casein, and peptide probes to indicate varying levels of inhibition of the pepsin enzyme. These assays were then used to screen the Library of Pharmacologically Active Compounds (LOPAC) and various other compounds suggested to us by outside sources. Once target compounds have been identified, they will be subjected to cell based assays to assess their viability as drug candidates in vivo