Cryptosporidium spp. and Toxoplasma gondii are also Category B biothreat agents because their infectious forms resist chemical inactivation and can be easily harvested and introduced into food and water supplies. Cryptosporidium are a major cause of prolonged and disabling diarrhea and Toxoplasma can cause a serious illness upon primary infection that is particularly dangerous to pregnant women. There is only one FDA- approved drug for cryptosporidiosis, and its efficacy is controversial. Therapeutic options for Toxoplasma are limited by toxicity. The C. parvum and T. gondii calcium dependent protein kinase 1 (Cp &TgCDPK1) can be selectively targeted with so-called Bumped Kinase Inhibitors (BKIs) that do not inhibit mammalian kinases, and these BKIs prevent the growth of cryptosporidium and toxoplasma. The BKIs have good oral bioavailability, pharmacokinetic, and are easy to synthesize. One of our lead BKIs has been shown to have efficacy in mouse models of cryptosporidiosis and toxoplasmosis. Thus BKIs are now excellent lead candidates for drug development for the therapy of cryptosporidiosis and toxoplasmosis. This proposal is to move the BKIs through pre-clinical development and select a clinical candidate. The goal of this project is to have a clinical candidate for the therapy of cryptosporidiosis and toxoplasmosis that is ready to undergo FDA IND review, with 1-2 compounds as backups.

Public Health Relevance

Cryptosporidium spp. are a major cause of prolonged disabling diarrhea, and there are only poorly efficacious drugs available now for Cryptosporidium treatment. Toxoplasma gondii causes disabling primary infection, and can endanger the fetus of pregnant women. Therapy for T. gondii is limited due to toxicity. This proposal is to test drug candidates, developed in another NIAID funded project, for cryptosporidiosis and toxoplasmosis to the point where they can be tested in humans. In the end, the goal is to have a drug candidate for regulatory (FDA) approval, with 1-2 compounds as backups.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI111341-01
Application #
8692204
Study Section
Special Emphasis Panel (ZAI1-AWA-M (J2))
Program Officer
Rogers, Martin J
Project Start
2014-03-15
Project End
2019-02-28
Budget Start
2014-03-15
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$1,580,174
Indirect Cost
$373,663
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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