Discovery of Novel Compounds that Enhance Enteric Nervous System Function

Unmet need
Necrotizing enterocolitis (NEC), a condition of newborns in which a portion of the bowel dies. NEC affects one in 1000-4000 births, or about 10% of preterm children and is associated with an overall mortality of up to 40%. NEC is thought to be caused by defective bacterial-host signaling during colonization of the intestine with bacteria, leading to an exaggerated inflammatory response. Currently, there is no specific cure for NEC, and surgical resection of the damaged tissue is often required. The overall survival for patients (70-80%) has not changed significantly in the past 30 years.
 
Technology Overview
Johns Hopkins researchers have identified novel agents that reduce NEC. By stimulating enteric glial cells, these compounds are able to inhibit Toll-like receptor 4 (TLR4 signaling) in the intestinal epithelium. TLR4 in turn plays a role in the pathogenesis of NEC.
 
Stage of Development
The inventors have tested the identified compounds and have shown that they are able to inhibit TLR4 signaling and NEC in vivo in mice and ex vivo in premature human NEC tissue. Studies of the compounds in murine and porcine models of NEC are currently ongoing.
 
Publications
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