Researchers awarded NIH grant to develop, test new drugs for treating Giardia infections

The microscopic parasite Giardia can be found within Idaho, every region of the U.S. and around the world. While Giardia is not considered fatal, anyone who has suffered from the diarrheal disease knows how uncomfortable it can be. In developing countries, it can cause dehydration and other serious complications in infants and children, which can lead to poor nutrient absorption, secondary infections and fatality. For this reason, researchers have long worked towards improving treatment methods for the infection.

Boise State researcher Ken Cornell counts himself among these researchers. Cornell, an associate professor in the Department of Chemistry and Biochemistry, and his collaborator John Thurston, an associate professor of chemistry at the College of Idaho, recently were awarded a three year, $418,000 grant from the National Institutes of Health to develop and test new anti-parasitic drugs to fight Giardia infections.

The university partnership grew out of an IDeA Network of Biomedical Research Excellence (INBRE) collaboration between Cornell and Thurston. Thurston, a synthetic chemist, will synthesize new drugs while Cornell and his team will examine how well the drugs work against the target enzyme and how well they work against cultures of parasites.

Cornell credits his career-long interest in parasitic research to his work as a Peace Corps volunteer in the 1980s.

"I worked at a bush school in Kenya and a lot of my students were routinely sick from parasitic diseases," he explained. "Many had reoccurring diarrheas, which, often were due to Giardia or amoebas, and the drugs to treat them were not readily available or were too expensive. My students would recover, but it was a very unpleasant infection that hampered their learning. In young kids, the diarrheal diseases caused by viruses, bacteria and parasites were a common cause of infant mortality by dehydration."

In the U.S., Giardia is often an underreported problem in institutionalized settings – for instance, in daycares, prisons and nursing homes. In outdoorsy communities like Boise, it also can be a problem for municipal water supplies.

"Giardial cysts are the infectious part and they can resist treatment with bleach," Cornell said. "You have to be cautious. It takes boiling, UV treatment, filtration or extensive contact with bleach to kill the cysts or remove them from the water. It's not easy. Since the cysts resist drying, they can persist on solid surfaces and in soil, which is why they can spread in institutional settings."

After the Peace Corps, Cornell went to graduate school with the goal of working on drugs and vaccines to treat infectious diseases. In many ways, he sees the NIH collaborative grant as an extension of the work he began as a doctoral student. He explains it also is an ideal project for training students who will be the next generation of biomolecular researchers.

"These projects are really amenable to training undergraduates, as the parasites we're studying are easy to grow and not terribly dangerous under the conditions we're using," Cornell said. "A lot of the work we do doesn't directly deal with pathogens, we're working with a particular enzyme within the pathogen, testing to see if compounds are going to be enzyme inhibitors."

Cornell's team currently consists of about 16 undergraduates and one graduate student in his lab working on various projects. These students are trained on every aspect of the drug development process, from cloning genes for potential Giardia target proteins, to synthesizing and testing inhibitors in enzyme assays, and testing their efficacy against live parasites grown in test tubes and in animal models of disease. This work especially is timely since there is concern that some strains of the parasite are becoming resistant to the main drug used to treat Giardia, metronidazole.

"We're seeing increasing treatment failures," Cornell said. "It's also a drug that not everyone can take – some people don't tolerate it very well, it's not good for pregnant women. We need new drugs for this."