Bumped-kinase inhibitor drug development for toxoplasmosis
Active Project Grant Awarded Last action
- Award ID
- R01HD102487
- Recipient
-
University Of Washington UEI HD1WMN6945W6
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $10,604,671
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 94% complete
- Originally
- Funding
-
- $9,903,368.00 Federal
- $701,303.00 Non-federal
- Place of performance
- Seattle, WA 98109, USA
Award details come from USAspending.gov.
Description
- Abstract
- Bumped-kinase inhibitor drug development for toxoplasmosis toxoplasma gondii infection is the most common known parasitic infection and causes systemic infections, particularly severe in immunocompromised humans, that damage the central nervous system. No clear beneficial therapy exists for pregnant women, who are experiencing new infections and possible fetal infection. Bumped-kinase inhibitors (bkis) target calcium-dependent protein kinase 1, necessary for cell entry and growth of t. Gondii. We have developed and shown proof-of-concept for treating toxoplasma gondii CNS infections and pregnancy infections with bkis. However, our late leads still have some issues such as optimal CNS penetration and metabolites associated with safety issues. In aim 1 of the proposed work, we will develop bkis that retain high systemic concentrations and distribution to both the central nervous system (CNS) and the fetus with acceptable safety attributes for use in pregnancy. This work will be aided by the extensive knowledge of our leads, computational predictions, and iterative experimentation addressing the few remaining issues. We will elucidate the pharmacodynamics and pharmacokinetics (PK/PD) associated with efficacious t. Gondii therapy, an area that hasn't been explored before in toxoplasmosis therapy. Once optimal bkis are obtained and the optimal PK/PD known, in aim 2 we will test BKI late leads for effects in rodent and ovine models of congenital toxoplasmosis. The pregnant mice t. Gondii congenital model will be useful for prioritizing compounds to further study in the pregnant sheep t. Gondii congenital model. The pregnant sheep t. Gondii congenital model is a superior model for human t. Gondii congenital therapy than the mouse model because of similarities in sheep and humans (VS. Mice) in length of gestation, numbers of fetuses per pregnancy, similarities in outcomes of congenital infection, and immune recognition of t. Gondii. Our deliverables will be late lead bkis, with demonstrated safety and efficacy in two animal models of congenital toxoplasmosis, to advance to GLP toxicity testing required for IND approval. Our likelihood for success is greatly improved by our collective knowledge from working on these compounds for cryptosporidiosis and the well-established scientific team together with advisors and consultants from our partners at path, abbvie, and bayer, who have decades of experience in pharmaceutical development.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $0 | $0 | |
| Amendment | $67,508 | $0 | |
| Amendment | $67,508 | $0 | |
| Amendment | $607,571 | $0 | |
| Amendment | $607,571 | $0 | |
| Amendment | $607,571 | $0 | |
| Amendment | $60,771 | $0 | |
| Amendment | $60,771 | $0 | |
| Amendment | $60,771 | $0 | |
| Amendment | $607,707 | $0 | |
| Amendment | $607,707 | $0 | |
| Amendment | $607,707 | $0 | |
| Amendment | $607,707 | $0 | |
| Amendment | $649,614 | $0 | |
| Amendment | $649,614 | $0 | |
| Amendment | $649,614 | $0 | |
| Amendment | $649,614 | $0 | |
| Amendment | $63,404 | $0 | |
| Amendment | $63,404 | $0 | |
| Amendment | $63,404 | $0 | |
| Amendment | $570,612 | $0 | |
| Amendment | $570,612 | $0 | |
| Amendment | $701,303 | $0 | |
| Original award | $701,303 | $701,303 |
Show all 24
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Portland VA Research Foundation, Inc. | $16,632 | |
| Universitat Bern | $16,415 | |
| Universidad Complutense De Madrid | $69,349 | |
| Universitat Bern | $16,416 | |
| Portland VA Research Foundation, Inc. | $16,632 | |
| Universidad Complutense De Madrid | $69,347 |
Quick answers
Who received award R01HD102487?
R01HD102487 was awarded to University Of Washington by National Institute of Child Health and Human Development (National Institutes of Health) on March 15, 2021.
How much is award R01HD102487 worth?
$10,604,671 has been obligated on R01HD102487: $9,903,368 in federal funding and $701,303 in non-federal funding.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award