Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms c...

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Veröffentlicht in:PLoS pathogens 2021-06, Vol.17 (6), p.e1009601-e1009601
Hauptverfasser: Bah, Germanus S, Schneckener, Sebastian, Hahnel, Steffen R, Bayang, Nicolas H, Fieseler, Helena, Schmuck, Gabriele M, Krebber, Ralph, Sarr, Anouk, Terjung, Carsten, Ngangyung, Henrietta F, Ekale, David D, Mfopit, Youssouf M, Rufener, Lucien, Graham-Brown, John, Tanya, Vincent N, Glenschek-Sieberth, Martin, Kulke, Daniel, Makepeace, Benjamin L
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container_end_page e1009601
container_issue 6
container_start_page e1009601
container_title PLoS pathogens
container_volume 17
creator Bah, Germanus S
Schneckener, Sebastian
Hahnel, Steffen R
Bayang, Nicolas H
Fieseler, Helena
Schmuck, Gabriele M
Krebber, Ralph
Sarr, Anouk
Terjung, Carsten
Ngangyung, Henrietta F
Ekale, David D
Mfopit, Youssouf M
Rufener, Lucien
Graham-Brown, John
Tanya, Vincent N
Glenschek-Sieberth, Martin
Kulke, Daniel
Makepeace, Benjamin L
description Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.
doi_str_mv 10.1371/journal.ppat.1009601
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source Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Directory of Open Access Journals; PubMed Central Open Access
subjects Animal welfare
Anthelmintic agents
Anthelmintics
Antiparasitic agents
Biology and Life Sciences
Blindness
Cattle
Channels
Development and progression
Drug dosages
Drug therapy
FDA approval
Fecundity
Genomes
Ivermectin
Larvae
Medicine and Health Sciences
Nematodes
Onchocerca
Onchocerca volvulus
Onchocerciasis
Parasites
Patient outcomes
Potassium
Potassium channels
Research and Analysis Methods
Rivers
Sibling species
Signs and symptoms
Tropical diseases
title Emodepside targets SLO-1 channels of Onchocerca ochengi and induces broad anthelmintic effects in a bovine model of onchocerciasis
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