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.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Achtman AH,Pilat S,Law CW,Lynn DJ,Janot L,Mayer ML,Ma S,Kindrachuk J,Finlay BB,Brinkman FS,Smyth GK,Hancock RE,Schofield Ldoi
10.1126/scitranslmed.3003515subject
Has Abstractpub_date
2012-05-23 00:00:00pages
135ra64issue
135eissn
1946-6234issn
1946-6242pii
4/135/135ra64journal_volume
4pub_type
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