Murad credits advances in biochemistry with their discovery. "I always thought we would find a compound. We now have the right set of people and right circumstances to solve this. We found this compound while screening a library of chemical substances," Murad said.
This area of molecular medicine is called cell signaling.
"You start with one molecule of a toxin or a hormone," said Alexander Kots, Ph.D., the lead author and an instructor at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UT Health Science Center at Houston. "The toxin binds to a target and influences it. Soon you have 10 molecules, then 100, then 1,000 and so forth. This is called signal amplification. One molecule of toxin can produce millions of molecules of water."
Their strategy is to stop the signal amplification process early on, thereby halting enterotoxigenic diarrhea, said co-author Byung-Kwon Choi, Ph.D., a research fellow at the IMM.
"Various bacterial toxins are responsible for increasing the production of intracellular messenger molecules. These molecules contribute to the increase in fluid secretion. We discovered a compound that blocks one of the pathways responsible for ETEC diarrhea. This has never been done before," Murad said.
Besides diarrheal disease, this potential drug, based on its mechanism of action, could have promising effects in other diseases such as inflammatory bowel disease and some endocrine disorders, Murad said.
"The relatively easy chemical synthesis (single step) and a presumed low cost should make it very attractive for therapy of diarrhea in developing countries," Murad
|Contact: Robert Cahill|
University of Texas Health Science Center at Houston