New drug could help 500,000 gastrointestinal patients in the US
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Gastrointestinal infections from Clostridioides difficile (C. diff) affect about 500,000 people in the U.S. a year, 20,000 of which die. Now, a new study performed in mice may have found a solution for the condition.
Researchers have identified a compound that prevents C. diff infection caused by multiple strains of the bacterium and are using it to develop new drug candidates that target the disease.
This is according to a press release published on Sunday by the American Society for Biochemistry and Molecular Biology.
The antibiotics used to treat C. diff infection cause life-threatening diarrhea and only two major drugs are approved to treat the condition only after the infection has taken hold.
“C. diff infection is quite a burden to the U.S. healthcare system, costing $3 billion to $4 billion annually,” said Jacqueline Phan, a chemistry doctoral student in the lab of Ernesto Abel–Santos, a biochemistry professor at the University of Nevada, Las Vegas.
“Our research aims to create a preventative drug that could be used to treat susceptible individuals before the infection starts, instead of treating patients only after they display signs of the infection.”
“Some of the new compounds we have developed provide multiday protection in mice from just a single dose,” said Abel–Santos. “What’s more, we found that these compounds appear to move in a loop between the liver and the intestine, which means that the liver is enabling a slow release of these compounds to the gut.”
Forming dormant spores
C. diff has the notorious ability to form dormant spores that can survive on surfaces or in the gastrointestinal track and once they reach the nutrient-rich intestinal lumen germinate, turning into cells that cause symptomatic infection.
“Anthrax is another well-known spore-forming type of bacteria,” said Abel–Santos.
“After the anthrax attacks in 2001, I started thinking about how these spores — which are basically specks of sand — detect their environment and start the germination process that returns them to a normal living organism. I realized that targeting the germination process could be a way to prevent infectious diseases such as C. diff.”
To find a way to inhibit the spread of C. diff, the researchers studied compounds that thwarted spore germination at very low concentrations. They identified the aniline-substituted bile salt analog CaPA as the best candidate molecule.
CaPA did have one drawback: it isn’t stable enough to survive in the gut long enough to be used for prevention. The researchers therefore engineered a new generation of compounds that are similar to CaPA while being more stable.
“This is something that has not been studied before,” said Abel-Santos in the statement. “It might be possible to use the patient’s own liver as part of the treatment plan.”
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