University of Washington - PK/PD modeling for anti-Shigella drug candidates

Start : September 2017 | Status : Active

The scientists:
Dr. Samuel Arnold and Ms. McCloskey will focus their research on the setting up of an animal model of Shigella for assessing antibiotic efficacy and the integration of in vitro and in vivo data to generate a PBPK/PD model to enable the identification of novel anti-Shigella drug candidates. Samuel Arnold obtained his PhD in pharmaceutics from the University of Washington School of Pharmacy under the guidance of Dr. Nina Isoherranen. He has extensive background in pharmaceutical sciences including enzymology, pharmacology and clinical pharmacokinetics. He has recently contributed to the identification of gastrointestinal drug exposure as an important driver of anti-cryptosporidium drug efficacy.

Molly McCloskey graduated with a Bachelor of Science in Biology from Saint Vincent College, Latrobe, Pennsylvania. Since then, she has studied cellular architecture and the molecular components involved in single cell wound healing. She currently works in the Van Voorhis lab at the University of Washington, working on developing therapies for cryptosporidiosis and aiding in research of other infectious diseases.

The sponsor: University of Washington

Foundation funding: The Foundation is providing £199,874 in support.

GSK’s contribution: GSK will contribute its scientific expertise including DMPK support on lead drug candidates and access to PBPK/PD modeling resources.

Project Description: The project focuses on drug discovery for Shigella. Main challenges in development of anti-shigella drugs are the lack of suitable animal models to evaluate compounds and the lack of information on PK/PD to anticipate in vivo efficacy and human dose.

The first step in this project will be to test if the shigellosis B6 mouse model or other murine alternatives are suitable to evaluate antibiotics. Based on the localization of Shigella to the large intestine and the need to deliver antibiotics in GI tract, previous experience with PBPK-PD models to predict in vivo drug efficacy for anti-cryptosporidium drugs will be applied to predict in vivo efficacy of anti-Shigella compounds.