There is an immediate and dire need to rapidly identify and prioritize antimalarial drug combinations for clinical use. Combination therapy has the best chance of reducing the frequency at which new drug resistance phenomena emerge, and our preliminary data suggest that dozens of previously unrecognized drug combinations with high degrees of synergy can be rapidly identified by our new approach. We will leverage the considerable complementary expertise of five consortium laboratories to identify, prioritize and optimize novel combination drug therapy for drug resistant Plasmodium falciparum malaria. In this effort we will use state of the art high throughput screening capabilities of the National Center for Advanced Translational Science (NCATS), as well as a recently perfected in vitro apparatus that exposes P. falciparum to programmable, dynamically changing drug concentrations. We will also validate potentiation of both 48 hr parasite reduction and 28 day cure using an innovative pharmacodynamic mouse malaria model.

Public Health Relevance

Effective antimalarial therapy is threatened by delayed parasite clearance to the artemisinin class of drugs. This work will identify novel combinations of existing approved drugs which can either augment artemisinin killing while deterring artemisinin partner drug resistance or surpass the parasite killing rates of the artemisinins and the quinolines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI111962-01
Application #
8707702
Study Section
Special Emphasis Panel (ZAI1-FDS-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
$1,055,093
Indirect Cost
$128,489
Name
Georgetown University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057