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Penn Vet’s Boris Striepen Receives $1.8M Grant to Find Drugs against Deadly Diarrheal Disease in Infants

By: Martin Hackett Date: Jan 2, 2018

striepen-releaseAwarded by the Bill & Melinda Gates Foundation
(Photo credit: Andrew Tucker)

[January 2, 2018; Philadelphia, PA] – Boris Striepen, PhD, Professor of Pathobiology at the School of Veterinary Medicine at the University of Pennsylvania, has received a $1.8-million, three-year grant from the Bill & Melinda Gates Foundation to enable the development of drugs for cryptosporidiosis, a diarrheal disease caused by microscopic parasites.

According to the Centers for Disease Control and Prevention, cryptosporidiosis sickens approximately 750,000 people each year in the United States. Caused by Cryptosporidium, a microscopic parasite that is typically transmitted through contaminated water, the disease is the second leading cause of severe diarrhea in small children. Globally, diarrheal diseases claim the lives of over 800,000 children under the age of five each year. The disease can be particularly serious in children who are malnourished and in individuals who are immunocompromised either due to illness or medical treatments.

Striepen is a leader in the study of Cryptosporidium. Under the grant, he and his team will use a variety of molecular genetic approaches to support drug development efforts, focusing on the identification and validation of therapeutic targets to guide medicinal chemistry. The project will build upon the team’s breakthrough in establishing techniques for genetic manipulation of Cryptosporidium to produce parasites suitable for drug testing in vitro and in vivo. Striepen will seek to link drug candidates with their targets within the parasite. Understanding how drugs work is very helpful to further enhance their potency and to anticipate and avoid unwanted toxicity and side effects.

“We will develop rigorous tests to establish whether drug candidates truly act on the target they were designed to,” Striepen said. “We will establish how the metabolism of the parasite interacts with that of its human host cell and assemble a catalog of those functions that are essential to the survival of the parasite and thus good targets for intervention.”

To accomplish these goals, Striepen and his researchers will conduct several activities. Initially, they will focus on those parasite functions for which drug candidates are already available and under study. Next, they will establish a model of the parasite’s metabolism and identify biochemical vulnerabilities within that model. They will seek to understand the metabolites the parasites uses at different points in its lifecycle and whether those are made by the parasite or taken from the host. Lastly, they will use genome-wide knock out approaches to discover all those activities that are essential to the parasite’s viability.

“This information will allow us not only to understand the lifecycle in much greater detail,” said Striepen, “but also open the door to more sophisticated manipulation of the parasite, to support drug development, but also to potentially generate weakened strains that may be suitable for vaccination.”

Striepen joined Penn Vet’s faculty in July 2017. His research program is supported by the National Institutes of Health, the Bill & Melinda Gates Foundation, and the Wellcome Trust. Striepen serves on numerous scientific advisory and editorial boards including the Bernhard Nocht Institute for Tropical Medicine, Keystone Conferences, PLoS Biology, and MBio, and he was the director of the Biology of Parasitism summer research course at the Marine Biological Laboratories in Woods Hole. Striepen received his PhD at Philipps-Universität in Marburg, Germany and was a Post-doctoral Fellow at the University of Pennsylvania.