Developing novel antisecretory drugs to treat infectious diarrhea.

Diarrhea, a disease of poverty and poor sanitation, kills an estimated two million children each year. Oral rehydration therapy is a very simple and inexpensive treatment that has significantly reduced mortality from secretory diarrhea caused by rotavirus, cholera and enterotoxigenic Escherichia coli. The efficacy and adoption of oral rehydration therapy would be enhanced by a drug that reduces fluid loss associated with these diseases and alleviates disease symptoms. Secretion and absorption by the intestine offer a number of potential drug targets to reduce fluid loss. Among these, the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the most attractive because it is the primary driver of secretion in cases of diarrhea caused by enterotoxigenic bacteria. CFTR can be inhibited by both natural products and synthetic small molecules. iOWH032 is a synthetic CFTR inhibitor that has recently entered clinical trials for this indication.