ArticlePLoS neglected tropical diseases2017
Defining the target and the effect of imatinib on the filarial c-Abl homologue.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- The pipeline for drugs for control and elimination of neglected tropical diseases: 2. Oral anti-infective drugs and drug combinations for off-label use.Parasites & vectors · 2023Review
- Drug Repurposing and De Novo Drug Discovery of Protein Kinase Inhibitors as New Drugs against Schistosomiasis.Molecules (Basel, Switzerland) · 2022Review
- A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.Scientific reports · 2021Article
- High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni.Analytical and bioanalytical chemistry · 2021Article
- Drug-induced reactive oxygen species-mediated inhibitory effect on growth of Trypanosoma evansi in axenic culture system.Parasitology research · 2020Article
- The ABL kinase inhibitor imatinib causes phenotypic changes and lethality in adult Schistosoma japonicum.Parasitology research · 2019Article
- Evaluation of Different Concentrations of Imatinib on the Viability ofAdvanced biomedical research · 2019Article
- Mining Filarial Genomes for Diagnostic and Therapeutic Targets.Trends in parasitology · 2018Review
- Reduction of Loa loa Microfilaremia with Imatinib - A Case Report.The New England journal of medicine · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPreviously we demonstrated the micro- and macrofilaricidal properties of imatinib in vitro. Here we use electron and multiphoton microscopy to define the target of imatinib in the adult and microfilarial stages of Brugia malayi and assess the effects of pharmacologically relevant levels of imatinib on the adult parasites.
methodsAfter fixation of adult B. malayi males and females, sections were stained with polyclonal rabbit anti-c-Abl antibody (or isotype control) and imaged with multiphoton fluorescent microscopy. Microfilariae were fixed and labeled with rabbit anti-c-Abl IgG primary antibody followed by anti-rabbit gold conjugated secondary antibody and imaged using transmission electron microscopy (TEM; immunoEM). In addition, adult B. malayi males and females were exposed to 0 or 10μM of imatinib for 7 days following which they were prepared for transmission electron microscopy (TEM) to assess the drug's effect on filarial ultrastructure.
resultsFluorescent localization of anti-c-Abl antibody demonstrated widespread uptake in the adult filariae, but the most intense signal was seen in the reproductive organs, muscle, and intestine of both male and female worms. Fluorescence was significantly more intense in the early microfilarial stage (i.e. early morula) compared with later development stages (i.e. pretzel). Anti-c-Abl antibody in the microfilariae localized to the nuclei. Based on TEM assessment following imatinib exposure, imatinib appeared to be detrimental to embryogenesis in the adult female B. malayi.
conclusionsAt pharmacologically achievable concentrations of imatinib, embryogenesis is impaired and possibly halted in adult filariae. Imatinib is likely a slow microfilaricide due to interference in intra-nuclear processes, which are slowly detrimental to the parasite and not immediately lethal, and thus may be used to lower the levels of L. loa microfilariae before they are treated within the context of conventional mass drug administration.
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