This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Malaria remains one of the world s most devastating diseases, killing over 1 million children a year. The treatment of choice for malaria for over 50 years has been chloroquine (CQ) but the utility of this drug has been compromised by the increasing prevalence of CQ resistance worldwide. Consequently, the development of safe and effective antimalarials is a global health priority. Together with our colleagues at the Dept. of Tropical Medicine, TSPHTM, we have developed a series of 4 aminoquinolines active against chloroquine-resistant malaria caused by Plasmodium falciparum. We have previously tested a series of these compounds in a monkey model of human malaria, P. cynomolgi in the rhesus macaque, a model of human vivax malaria. One of the compounds we tested previously (AQ13) was found to be an efficacious blood schizonticide against a chloroquine resistant isolate in the monkeys, has completed Phase I human trials, and is currently being tested in phase II trials in Mali. We are now looking at the efficacy of other compounds which will can potentially be used in combination with AQ13.Using our monkey models we are now looking at how this class of compounds is metabolized by P450 enzymes in the liver. Because the P450 complement of the rhesus macaque is similar to that of humans, we are not only able to assess efficacy but have the ability to look at pharmacokinetic parameters, including absorption, bioavailability, AUC, rate of excretion, and other factors which may be predictive of the ability of these compounds to be used for treatment of human malaria.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-45
Application #
7348995
Study Section
Special Emphasis Panel (ZRR1-CM-9 (01))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
45
Fiscal Year
2006
Total Cost
$30,971
Indirect Cost
Name
Tulane University
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
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Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

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