Effective Adjunctive Therapy by an Innate Defense Regulatory Peptide in a Preclinical Model of Severe Malaria
- Author(s)
- Achtman, AH; Pilat, S; Law, CW; Lynn, DJ; Janot, L; Mayer, ML; Ma, SH; Kindrachuk, J; Finlay, BB; Brinkman, FSL; Smyth, GK; Hancock, REW; Schofield, L;
- Details
- Publication Year 2012-05-23,Volume 4,Issue #135,Page 135ra64
- Journal Title
- SCIENCE TRANSLATIONAL MEDICINE
- Publication Type
- Journal Article
- 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.
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Keywords
- TUMOR-NECROSIS-FACTOR; PLASMODIUM-FALCIPARUM MALARIA; EXPERIMENTAL CEREBRAL MALARIA; MONOCLONAL-ANTIBODY; MONONUCLEAR-CELLS; IMMUNE-RESPONSE; MURINE MALARIA; IFN-GAMMA; T-CELLS; CHILDREN
- Research Division(s)
- Infection And Immunity; Bioinformatics; Cancer And Haematology
- Publisher's Version
- https://doi.org/10.1126/scitranslmed.3003515
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Creation Date: 2012-05-23 12:00:00