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Related Experiment Videos

Screening compounds for sleeping sickness therapy without relapse.

W E Ormerod1, B H Raseroka

  • 1London School of Hygiene and Tropical Medicine.

Bulletin De La Societe De Pathologie Exotique Et De Ses Filiales
|January 1, 1988
PubMed
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Degeneration of serotonin-specific neurons in the brain in experimental Trypanosoma brucei infection.

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Is Trypanosoma brucei an intracellular parasite?

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Interaction between Trypanosoma brucei and the ependymal cell of the choroid plexus.

Transactions of the Royal Society of Tropical Medicine and Hygiene·1986
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Transactions of the Royal Society of Tropical Medicine and Hygiene·1986

New screening methods for sleeping sickness drugs are needed. Bleomycin shows promise as a single-agent treatment, effectively clearing Trypanosoma brucei from all tested sites.

Area of Science:

  • Parasitology
  • Neuroscience
  • Pharmacology

Background:

  • Trypanosoma brucei has an intracellular stage within ependymal cells of the choroid plexus and ventricle lining.
  • Standard drug treatments often fail to eliminate these "occult" parasitic stages.
  • This necessitates novel screening techniques for effective trypanocidal compounds.

Purpose of the Study:

  • To introduce and validate a new in vivo screening method for trypanocidal drugs.
  • To assess the efficacy of various compounds against Trypanosoma brucei in different anatomical sites, including the central nervous system.
  • To identify promising drug candidates for treating human African trypanosomiasis (sleeping sickness).

Main Methods:

  • A novel drug screening technique was employed using infected (donor) and clean (recipient) mice.

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  • Donor mice, infected for 28 days, received drug treatments.
  • Samples from blood, cerebral cortex, choroid plexus, and ventricle lining of donor mice were injected into recipient mice to assess parasite clearance.

    • Main Results:

    • Suramin cleared parasites from blood and cerebral cortex but not from ependymal cell sites.
    • Melarsoprol showed activity across all sites but lacked consistent efficacy.
    • DFMO cleared ependymal cells, while metronidazole combined with suramin demonstrated activity in all tested areas. Bleomycin emerged as the most effective single agent.

    Conclusions:

    • Bleomycin, an existing anti-cancer drug, demonstrates significant potential for clinical evaluation against sleeping sickness.
    • The developed screening method effectively differentiates drug activity across various anatomical compartments, including CNS-associated sites.
    • Further investigation into potential drug interactions, such as the incompatibility of bleomycin with DFMO, is warranted.