Kovi Bessoff, a University of Vermont College of Medicine M.D.-Ph.D. student, received a Young Investigator Award at the American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting held in Atlanta, Ga., on Nov. 11, 2012.
Designed to encourage developing young scientists to pursue careers in various aspects of tropical disease research, the award is presented to outstanding young researchers during the ASTMH Annual Meeting. Bessoff discussed his research on “Improving Therapeutics for the Treatment of Cryptosporidiosis using High Throughput Methods” as part of the Young Investigator Award program at the conference.
“We study a parasite called Cryptosporidium parvum, which, along with another closely related parasite, causes a diarrheal disease known as cryptosporidiosis,” says Bessoff. “The disease is a leading cause of diarrhea in the developing world, and is particularly devastating to AIDS patients and little children. Currently, there are no vaccines or effective treatments available.”
Bessoff has been working with mentor Christopher Huston, M.D., associate professor of medicine, since 2010. According to Huston, there is little incentive for the pharmaceutical industry to develop treatments for the developing world and methods to work on Cryptosporidium parasites are severely lacking.
“To address both of these issues, Kovi took a ‘drug repurposing approach’ – focusing on identification of drugs already approved for other uses that can possibly be used to treat cryptosporidiosis,” explains Huston.
The approach paid off. Bessoff developed the first high-throughput cell-based screening assay to identify drugs that inhibit growth of Cryptosporidium parvum within intestinal epithelial cells. Then, using his unique method to screen a library of drugs, he was able to identify 16 drugs that inhibit Cryptosporidium growth.
“We discovered that the cholesterol-lowering drug pitavastatin has good activity against the parasite,” Bessoff says. “We believe that it inhibits Cryptosporidium parvum growth by the same mechanism that it employs to reduce cholesterol levels and think this provides sufficient evidence to conduct human clinical trials of pitavastatin for the treatment of cryptosporidiosis.”
Proud mentor Huston is excited about the potential of these candidate drugs for treatment of cryptosporidiosis.
“A great deal is known about the mechanism of action for many of the drugs, because of the compound libraries that we chose to screen, and this enabled us to formulate hypotheses about how they affect Cryptosporidium parasites,” he says. “Kovi followed-up on one of the most interesting drug leads, which is an inhibitor of the host cell enzyme HMG-CoA reductase.”
In collaboration with Adam Sateriale, another Cellular, Molecular and Biomedical Sciences graduate student also working in Huston’s lab, Bessoff used the drug and a bioinformatics analysis of the Cryptosporidium genome to prove that Cryptosporidium parvum is dependent on host cell synthesis of isoprenoid precursors. The team determined that the parasite appears to require isoprenoids for many biochemical processes, but cannot synthesize them itself.
Huston credits Bessoff with not only identifying potential treatments for Cryptosporidiosis, but also elucidating critical information about Cryptosporidium biology that can be shared with scientists in the field.