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

Ariel H. Achtman, Sandra Pilat, Charity W. Law, David J. Lynn, Laure Janot, Matt L. Mayer, Shuhua Ma, Jason Kindrachuk, B. Brett Finlay, Fiona S L Brinkman, Gordon K. Smyth, Robert E W Hancock, Louis Schofield

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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.

Original languageEnglish
Article number135ra64
JournalScience Translational Medicine
Issue number135
Publication statusPublished or Issued - 23 May 2012

ASJC Scopus subject areas

  • Medicine(all)

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