The goal of this project is to develop a small molecule drug as a novel therapeutic for the modulation of gutdysbiosis in patients with inflammatory bowel disease (IBD). Over 1.6 million Americans suffer from IBD, anumbrella term used to describe chronic inflammation of all or part of the digestive tract, including Crohn's diseaseand ulcerative colitis. IBD is a complex immune disorder that can be caused by genetics, environment, aberrantimmune response and disruption of the digestive tract microbiota. IBD ranks as one of the five most expensiveGI disorders, with an annual direct medical cost burden between 11 and 28 billion dollars, approximately half ofwhich are for prescription drugs. Current strategies to manage or treat IBD involve suppressing the immunesystem, however many of these drugs are not intended for long term use, and others have no effect in up to halfof patients treated. Therefore, currently available therapies do not meet the needs of all patients and newtreatment approaches are needed. Symberix, Inc. is developing a novel class of small molecule drugs thatspecifically target and inhibit one of the known causes of digestive tract inflammation: the microbiome. Pilotstudies demonstrate the preliminary feasibility of blocking the activity of bacterial beta glucuronidases (GUSenzymes) and slowing the growth of harmful bacteria without compromising the growth of protective bacteria.Small molecule GUS inhibitors also show potent activity in ex vivo assays using biological samples derived frompatients with IBD. This Phase I proposal will focus on confirming and extending pilot studies by rigorouslyevaluating the biological activity of two candidate small molecule drugs in an in vivo mouse model of ulcerativecolitis and an ex vivo inhibition assay using IBD patient-derived stool samples.
Public Health Relevance Statement: Project Narrative
Existing treatments for inflammatory bowel disease (IBD) work by targeting inflammatory pathways in the human
body. This project aims to develop novel small-molecule drugs with a unique mechanism of action that selectively
targets pro-inflammatory bacteria in the gut. Non-antibiotic drugs that target disease pathways in the gut
microbiome represent a new treatment paradigm for IBD and is expected to complement existing host-specific
treatments.
Project Terms: <21+ years old> 