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Compounds could solve world's infection problems

PROVO — It's an unpleasant topic, but for children in third-world countries, diarrhea is more than just uncomfortable, it can be life-threatening."What's happening is these organisms are thriving in the gastrointestinal tract, then the children end up with these infections and have a hard time absorbing nutrients, and it's a major cause of death," said Paul Savage, BYU professor of chemistry and bio-chemistry. "If you could effectively restart their GI function with the right type of bacteria, then it would eliminate a lot of suffering and certainly a lot of death."And that's just what Savage is working on.Because bacteria are everywhere in and around us, our bodies use antimicrobial agents to keep them in check.But not everyone's "agents" are strong enough to keep the germs under control.So Savage created ceragenins, patented compounds that mimic the body's own antimicrobial agents and fight off bacteria, without the bacteria becoming resistant, a problem created when antibiotics are used for too long.It's those ceragenins that would be the key to eliminating germs that cause diarrhea."They're fairly easy to make, stable and they're very good at killing bacteria," he said. "We expect to be able to use them in the same areas in which the body's natural defense are used, to either augment activity or replace deficiencies."After three years, and thanks to his recent $2.9 million grant from the National Institutes of Health, Savage hopes to be in clinical trials.The ceragenins would be taken through a pill, and would stay in the GI tract without traveling to the rest of the body, Savage said.After they kill all the harmful agents, natural, good bacteria would need to be reintroduced, he said, most likely through another pill."It would be fast," he said. "Maybe the course of one or two days, take a couple of pills...then everything's wiped out and you start again fresh."For those with weaker immune systems and a lessened ability to produce their own antimicrobial agents, continued GI tract "maintenance" might be needed, Savage said."But one of the nice things is, (ceragenins) are very stable and they're relatively inexpensive to prepare, so you would imagine they would be useful in developing countries."Savage is also pairing with Dr. Roy Bloebaum at the Bone and Joint Research Lab at the VA Hospital to use ceragenins as a protective coating for medical devices.For the last 30 years, medical devices like metal plates, rods or tubes have been coated with antibiotics to prevent the growth of germs.However, antibiotics often failed to prevent or eliminate biofilms — massive growths of bacteria that clump together on a surface.But ceragenins were quick to eliminate the growths."From what we've seen they're pretty amazing," said Dustin Williams, a graduate student in bio-engineering working with Bloebaum.One of Williams' recent projects involved exposing a ceragenin-coated piece of metal to a biofilm, which killed nearly 10 billion bacteria in 24 hours. Antibiotics only reduced the amount to roughly 1 million, he said."Preventing biofilm from forming is very important, but we're also showing that even if bacteria that already reside in a biofilm touch the (coated) device, they'll be killed," Williams said.The technology has incredible potential for reducing infection, he said."I'm a graduate student," he said. "I could be entering into a field that could really take off."


E-mail: sisraelsen@desnews.com