In a development that may lessen the epidemic of diarrhea-related deaths among children in developing countries, scientists in the laboratory of Nobel Laureate Ferid Murad, M.D., Ph.D., at The University of Texas Health Science Center at Houston have discovered a novel compound that might lead to an inexpensive, easy-to-take treatment. The results of pre-clinical tests have now been published The compound - a pyridopyrimidine derivative - 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 diarrhea.
Diarrhea kills an estimated 1.6 to 2.5 million children every year, according to researchers quoted in the Bulletin of the World Health Organization. Enterotoxigenic strains of bacteria may account for a significant amount of these deaths, according to an article in Clinical Microbiology Reviews. Enterotoxigenic E. coli or ETEC is a leading cause of bacterial diarrhea.
Murad earned a Nobel Prize in Medicine in 1998 for the discovery of nitric oxide's role in cardiovascular disorders. His previous work with nitric oxide led to novel therapies for hypertension, angina, pulmonary hypertension and erectile dysfunction. Studies by his laboratory and others continue to examine possible applications of nitric oxide biology to stroke, blood clotting, septic shock and cancer, but most of this latter work is at a very early stage.
Other contributors to the study include: Scott R. Gilbertson, Ph.D., the Robert A. Welch Distinguished University Chair in Chemistry and the director of the Program in Chemical Biology in the Department of Pharmacology and Toxicology at the University of Texas Medical Branch at Galveston, and UTMB colleague Maria E. Estrella Jimenez; and Cirle Warren, M.D., assistant professor of medicine at the University of Virginia School of Medicine, and Guerrant.
An international patent application for the use of this compound to treat secretory diseases is pending.
Financial support was provided by The Welch Foundation, The Dunn Foundation, The National Institutes of Health, the Department of Defense and The University of Texas Health Science Center at Houston.