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"Bacterial toxin-induced diarrhoea probably kills in the ballpark of 2 million people a year (globally). Most of them are children less than 5 years old or senior people, and they become dehydrated," said Dr Ferid Murad of the University of Texas in Houston.
"It's often because of contaminated water or food supply," and most deaths occur in developing countries, Murad said.
Bacteria that attack the lining of the intestines stimulate the secretion of massive amounts of salts and water, depleting the body of needed fluids.
Murad and colleagues have found a chemical compound that could help keep the body from secreting fluids and salts in response to the infection.
The compound - known as a pyridopyrimidine derivative - works by interfering with cell communication, in effect blocking the signal to secrete excess fluids.
"I think it could be a very important contribution," said Murad, winner of the 1998 Nobel Prize in Medicine for discovering the role of nitric oxide in the cardiovascular system.
His discovery led to new treatments for high blood pressure, chest pain and erectile dysfunction, but he said his latest discovery may have even greater impact.
"The question will be, can we make a drug out of this and what will it take to do that?" said Murad, whose findings were published in the journal Proceedings of the National Academy of Sciences.
Looking to developing world
Another expert at the university said the findings show promise.
"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 travellers to the tropics and subtropics," Dr Herbert DuPont, an expert in infectious diseases, said in a statement.
In bacterial diarrhoea, bacteria multiply in the intestinal tract where they release toxins that raise levels of cell messengers known as cyclic nucleotides. These messengers tell intestinal cells to secrete salt and water.
No other drug of its kind
There are no current treatments that directly interfere with this process, Murad said. Most simply try to replace lost fluids to prevent dehydration.
"We figured out the mechanism many years ago and I've always thought this would be a wonderful opportunity to find a drug to block that pathway," said Murad, who formerly headed new drug discovery for Abbott Laboratories Inc.
He and colleagues tested different chemicals to see if they could find one that might interfere with the body's response to bacterial toxins. "Sure enough, we did."
The compound reduced the secretion of fluids and salts in rabbits injected with the toxin. Tests in mice suggest it is safe, Murad said.
In addition to helping children in developing countries, Murad thinks the compound may be useful as a pill to fend off traveller's diarrhoea. And it may help with inflammatory bowel disease, but that needs to be tested, he said.
Murad has applied for a patent on the compound and now hopes to secure funding to start human trials.
"To get this thing into a clinical trial to test the proof of concept that it does indeed work in humans will take a couple million dollars and a couple of years," he said. "But I am determined to do it because it is so important." – (Julie Steenhuysen/Reuters Health)
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June 2008
