ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Autophagy in protists and their hosts: When, how and why?Autophagy reports · 2023Article
- Plasmodium's fight for survival: escaping elimination while acquiring nutrients.Trends in parasitology · 2022Review
- Red Blood Cell BCL-xMicroorganisms · 2022Article
- Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria.Frontiers in cellular and infection microbiology · 2022Review
- Host-directed therapy, an untapped opportunity for antimalarial intervention.Cell reports. Medicine · 2021Review
- Review
- Elucidating Spatially-Resolved Changes in Host Signaling DuringFrontiers in cellular and infection microbiology · 2021Article
- Targeting liver stage malaria with metformin.JCI insight · 2019Article
- Discovery of Druggable Host Factors Critical to Plasmodium Liver-Stage Infection.Cell chemical biology · 2019Article
- Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection.Cell reports · 2019Article
- Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective.Frontiers in immunology · 2019Review
- Cancer-malaria: hidden connections.Open biology · 2018Article
- Opportunities for Host-targeted Therapies for Malaria.Trends in parasitology · 2018Review
- Identifying host regulators and inhibitors of liver stage malaria infection using kinase activity profiles.Nature communications · 2017Article
- The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria.Frontiers in microbiology · 2017Review
- HGF Secreted by Activated Kupffer Cells Induces Apoptosis ofFrontiers in immunology · 2017Article
- Host AMPK Is a Modulator of Plasmodium Liver Infection.Cell reports · 2016Article
- Current therapies and future possibilities for drug development against liver-stage malaria.The Journal of clinical investigation · 2016Review
- Malaria modeling: In vitro stem cells vs in vivo models.World journal of stem cells · 2016Review
- Why should cell biologists study microbial pathogens?Molecular biology of the cell · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Eliminating malaria parasites during the asymptomatic but obligate liver stages (LSs) of infection would stop disease and subsequent transmission. Unfortunately, only a single licensed drug that targets all LSs, Primaquine, is available. Targeting host proteins might significantly expand the repertoire of prophylactic drugs against malaria. Here, we demonstrate that both Bcl-2 inhibitors and P53 agonists dramatically reduce LS burden in a mouse malaria model in vitro and in vivo by altering the activity of key hepatocyte factors on which the parasite relies. Bcl-2 inhibitors act primarily by inducing apoptosis in infected hepatocytes, whereas P53 agonists eliminate parasites in an apoptosis-independent fashion. In combination, Bcl-2 inhibitors and P53 agonists act synergistically to delay, and in some cases completely prevent, the onset of blood stage disease. Both families of drugs are highly effective at doses that do not cause substantial hepatocyte cell death in vitro or liver damage in vivo. P53 agonists and Bcl-2 inhibitors were also effective when administered to humanized mice infected with Plasmodium falciparum. Our data demonstrate that host-based prophylaxis could be developed into an effective intervention strategy that eliminates LS parasites before the onset of clinical disease and thus opens a new avenue to prevent malaria.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.