Crippling 'Crypto'

Faculty Researcher Cuny Earns $3.8M NIH Grant to Develop Novel Therapeutics Against Cryptosporidium Parasite Infection

UH College of Pharmacy Assistant Professor Gregory D. Cuny, Ph.D., has been awarded a five-year, $3.8 million National Institutes of Health R01 grant to advance the development of novel therapeutics against infection by Cryptosporidium species of protozoan parasites.

Commonly used anti-parasitic drugs are ineffective, the only FDA-approved drug is poorly efficacious (or not at all in some immunocompromised populations), and no vaccine exists for cryptosporidiosis. Among otherwise healthy individuals, cryptosporidiosis can cause acute and chronic severe diahrrea and gastrointestinal pain. Among the immunocompromised, the cryptosporidiosis can be a life-threatening infection.

Cryptosporidium also has been identified as a potential bioterrorism agent due to its relative ease of dispersal and trasmission via ingestion of contaminated food and water or direct contact with contaminated soil, water or an infected host; the persistence of its oocyst form — a hardy, thick-walled stage of the parasite's life cycle — in soil or water for months; and the current lack of vaccines and effective therapeutics or filtration processes for the chlorine-resistant oocysts.

Crypto outbreaks have been reported worldwide, with the largest documented waterborne outbreak in U.S. history affecting 400,000 and at least partly contributing to about 80 deaths in Milawaukee, Wis., in 1993. The financial impact of the Milwaukee outbreak was an estimated $93 million in combined healthcare costs and productivity loss.

In the new R01 project, Cuny and his collaborators are continuing their work in the design and in-vitro evaluation of CpIMPDH inhibitors in assays of CpIMPDH inhibitory potency and selectivity, a C. parvum cell culture infection model and their absportion, distribution, metabolism and excretion properties. The project also will assess the in vivo pharmacokinetic and acute toxicity properties of CpIMPDH inhibitors and evaluate optimized CpIMPDH inhibitors in animal models of cryptosporidiosis.

Cuny’s team — which includes UHCOP Professor Ming Hu, Ph.D., Brandeis University's Liz Hedstrom, Ph.D., Emory University's Jan Mead, Ph.D., and the University of Georgia's Boris Striepen, Ph.D. — also will examine the impact of the inhibitors on commensal bacterial populations and develop a strategy for enterohepatic recycling to maximize gastrointestinal concentrations while reducing systemic exposure and toxicity risk.