Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria

Achtman, Ariel H., Pilat, Sandra, Law, Charity, Lynn, David J., Janot, Laure, Mayer, Matt L., Ma, Shuhua, Kindrachuk, Jason, Finlay, B. Brett, Brinkman, Fiona S.L., Smyth, Gordon K., Hancock, Robert E.W., and Schofield, Louis (2012) Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria. Science Translational Medicine, 4 (135). pp. 1-10.

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Abstract

Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defense regulator (IDR) peptides, based on host defense peptides. The Plasmodium berghei ANKA model of experimental cerebral malaria was adapted to use as a preclinical screen by combining late-stage intervention in established infections with advanced bioinformatic analysis of early transcriptional changes in co-regulated gene sets. Coadministration of IDR-1018 with standard first-line antimalarials increased survival of infected mice while down-regulating key inflammatory networks associated with fatality. Thus, IDR peptides provided host-directed adjunctive therapy for severe disease in combination with antimalarial treatment.

Item ID: 35856
Item Type: Article (Research - C1)
ISSN: 1946-6242
Funders: National Institutes of Health (NIH), Canadian Institutes of Health Research, National Health and Medical Research Council (NHMRC), Genome Canada (GC)
Projects and Grants: NIH program Grand Challenges in Global Health Research, GC Pathogenomics of Innate Immunity (PI2) Project
Date Deposited: 30 Oct 2014 23:56
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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