Research ArticleMalaria

Effective Adjunctive Therapy by an Innate Defense Regulatory Peptide in a Preclinical Model of Severe Malaria

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Science Translational Medicine  23 May 2012:
Vol. 4, Issue 135, pp. 135ra64
DOI: 10.1126/scitranslmed.3003515

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A Screening Room for Cerebral Malaria Drugs

Smart-phone retailers claim that their device brings the cinema to you. Yet, there’s something to be said for ambiance: A blockbuster film delivers more effective entertainment when screened in high-def surround sound versus on a 6-inch screen in a jammed subway car. Screening new drugs is no different. Although in vitro drug-screening models are convenient, it’s attention to pathophysiological details that creates an informative and predictive drug-screening platform. Achtman et al. now repurpose a mouse model of experimental cerebral malaria (ECM) to screen for adjuvant therapy against severe malaria.

Although first-line antimalarial drugs may control parasitemia, they do little to quell the inflammation that leads to seizures, coma, and long-term sequelae in patients with severe malaria. The authors hypothesized that innate defense regulator (IDR) peptides—host-derived signaling molecules that modulate the innate immune system—would serve as anti-inflammatory adjuvant therapy for ECM in combination with first-line drugs. The authors adapted the murine Plasmodium berghei ANKA ECM model to serve as a preclinical drug-screening platform by combining antimalarial drug intervention in established malarial infections with iterative mouse-human bioinformatic analysis. When co-administered with first-line antimalarial drugs, the IDR peptide down-regulated inflammatory networks and improved mouse survival. If these data translate to humans, IDR peptides could provide an anti-inflammatory adjuvant therapy for severe malaria and perhaps other infectious diseases.

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