New compound may make for inexpensive, easy-to-take diarrhea treatment

Washington, June 17 : Researchers in the US have discovered a novel compound that might lead to an inexpensive, easy-to-take treatment for diarrhoea, a major cause of child deaths in developing nations.

Researchers in the laboratory of Nobel Laureate Ferid Murad, M.D., Ph.D., at The University of Texas Health Science Center at Houston, have conducted pre-clinical tests of this compound, a pyridopyrimidine derivative.

This compound targets acute secretory diarrhea caused by E. coli and other enterotoxigenic strains of bacteria, which produce toxins that stimulate the linings of the intestines, causing them to secrete excessive fluid, thereby producing diarrhoea.

Enterotoxigenic E. coli or ETEC is a leading cause of bacterial diarrhea.

At the time of pre-clinical tests, the compound was linked with a significant reduction in intestinal fluid secretion in an animal model of bacterial diarrhea. It was also linked to reduced fluid build up during laboratory tests on human colon cells. It caused significant decrease in fluid secretion without apparent toxicity.

This method for treating enterotoxigenic diarrhea works by interrupting the diarrhea-causing chain of events that occur when bacterial toxins enter the intestinal tract.

The compound slows the transmission of information in the epithelial cells lining the intestines. Thus, the molecular mediators regulating the secretion of salt and fluid in the gut do not get fully activated. ETEC comes from faeces-contaminated food or water and also causes travellers' diarrhoea.

"This newly discovered compound decreases the formation of ever-present cellular messenger molecules, cyclic guanosine monophosphate and cyclic adenosine monophosphate, caused by various bacterial toxins and might prevent or attenuate the intestinal fluid secretion, diarrhoea and dehydration. While this research looks extremely promising as a preventive or therapeutic intervention in Third World diarrhoeal disease and travellers' diarrhoea, much work remains to be done to move into clinical trials and eventual therapeutic approval," said Murad, the senior author.

Murad said that in case of a natural catastrophe, this potential diarrhoea treatment could be used to treat outbreaks of enterotoxigenic E. coli caused by contaminated food and water supplies. The compound can be placed in a pill for adults and in a liquid for children.

There is another type of diarrhoea called secretory diarrhoea describes the condition when the small intestine, which is normally an absorptive organ, is stimulated to secrete salts and water into the intestinal lumen, often in massive quantities. The resulting diarrhoea can lead to profound fluid loss, dehydration, shock and death.

"Current antidiarrheal therapy is less physiologic, often working through inhibition of intestinal movement leading to potential complications. A drug that stops the loss of fluid and salt from the intestine could save infant lives in developing regions and alleviate suffering that would otherwise be experienced by travelers to the tropics and subtropics," said DuPont.

The study appears in the latest online edition of the journal Proceedings of the National Academy of Sciences of the United States of America.

ANI