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

Sci Transl Med. 2012 May 23;4(135):135ra64. doi: 10.1126/scitranslmed.3003515.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / therapeutic use*
  • Antimicrobial Cationic Peptides / therapeutic use*
  • Cells, Cultured
  • Female
  • Malaria / drug therapy*
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium berghei / drug effects
  • Plasmodium berghei / pathogenicity


  • Antimalarials
  • Antimicrobial Cationic Peptides
  • innate defense regulating peptide 1018

Associated data

  • GEO/GSE32007