University of Virginia Health System

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U.VA. RECEIVES GRANT FOR E. COLI RESEARCH

Toxins from the common bacteria Escherichia coli (E. coli) are responsible for outbreaks of food-borne illness around the world. In the U.S., an estimated 73,000 cases of infection and 61 deaths occur every year, according to the Centers for Disease Control and Prevention. E. coli is also the leading cause of acute kidney (renal) failure in young children, who can die from a complication called hemolytic uremic syndrome (HUS), in which red blood cells are destroyed and the kidneys fail. Now, researchers at the University of Virginia Health System are leading a multi-center study to develop new drugs to prevent pathogenic E. coli diseases like HUS. The long-term goal is to reduce the inflammation of kidney cells that can be a deadly after-effect of E. coli infection.

Tom Obrig, Ph.D., professor of research in U.Va.’s division of nephrology, has received a $2.8 million grant from the National Institutes of Health to develop new therapies for hemolytic uremic syndrome (HUS) over five years, in partnership with Charlottesville-based Adenosine Therapeutics, LLC.

“We hope to bring to the clinical testing stage a therapeutic intervention for this type of acute renal failure,” Obrig said. “Specifically, we will be examining adenosine-based compounds for anti-inflammatory activity that could prevent the renal failure associated with E. coli before it happens.” Recent mouse studies of HUS indicate that adenosine compounds can reduce the inflammation associated with E. coli toxins.

“The real emphasis from the NIH today,” Obrig explained, “is on developing new therapies by getting basic research to clinical use quickly. That’s what we’re doing with this grant on preventing E. coli-associated kidney failure. “

Obrig said there is a “window of opportunity” to treat patients early with adenosine-based, anti-inflammatory drugs when they come to their doctor or the emergency room suffering from hemorrhagic colitis, or bloody diarrhea, one complication of E. coli disease.

“If we can successfully treat them with adenosine and stop the inflammation that leads to kidney failure we could potentially save lives,” Obrig said. So far, no one knows why the toxins associated with E. coli bacteria target the kidneys and lead to renal failure. “But it can happen to anybody at any age. We’ll be working to stop that progression,” Obrig said.

Researchers hope to report to the Food and Drug Administration in one year about their findings, which could lead to clinical trials of an adenosine therapy for E. coli diseases.

July 29, 2003