Journal article
Effective adjunctive therapy by an innate defense regulatory peptide in a preclinical model of severe malaria
AH Achtman, S Pilat, CW Law, DJ Lynn, L Janot, ML Mayer, S Ma, J Kindrachuk, BB Finlay, FSL Brinkman, GK Smyth, REW Hancock, L Schofield
Science Translational Medicine | Published : 2012
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-li..
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Funding Acknowledgements
Supported by the Grand Challenges in Global Health Research program through the Foundation for the NIH and Canadian Institutes for Health Research (S.P., D.J.L., M.L.M., J.K., F.S.L.B., R.E.W.H., and L.S.), National Health and Medical Research Council (NHMRC) grants (L.S. and G.K.S.) and research fellowships (G.K.S. and L.S.), and Genome Canada through the Pathogenomics of Innate Immunity (PI2) project (D.J.L., J.K., F.S.L.B., and R.E.W.H.). L.S. and B.B.F. are International Research Scholars of the Howard Hughes Medical Institute. R.E.W.H. holds a Canada Research Chair. D.J.L. was supported by a Postdoctoral Trainee Award from the Michael Smith Foundation for Health Research (MSFHR) and F.S.L.B. is an MSFHR Senior Scholar. J.K. held a postdoctoral fellowship from the Canadian Cystic Fibrosis Foundation. C.W.L. holds a Melbourne Research Scholarship from the University of Melbourne. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.