ArticlePLoS neglected tropical diseases2019
In vivo kinetics of Wolbachia depletion by ABBV-4083 in L. sigmodontis adult worms and microfilariae.
Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Preclinical animal models for onchocerciasis and loiasis: A systematic review of applications in drug screening.PLoS neglected tropical diseases · 2026Pooled it
- Fexinidazole and Corallopyronin A target Wolbachia-infected sheath cells present in filarial nematodes.PLoS pathogens · 2025Article
- Fexinidazole and Corallopyronin A targetbioRxiv : the preprint server for biology · 2025Article
- Combinations of the azaquinazoline anti-Frontiers in microbiology · 2024Article
- A Phase-I pharmacokinetic, safety and food-effect study on flubentylosin, a novel analog of Tylosin-A having potent anti-Wolbachia and antifilarial activity.PLoS neglected tropical diseases · 2023Article
- Multiple lineages of nematode-Wolbachia symbiosis in supergroup F and convergent loss of bacterioferritin in filarial Wolbachia.Genome biology and evolution · 2023Article
- Filariasis research - from basic research to drug development and novel diagnostics, over a decade of research at the Institute for Medical Microbiology, Immunology and Parasitology, Bonn, Germany.Frontiers in tropical diseases · 2023Article
- The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration.Parasites & vectors · 2023Review
- Discovery of Substituted Di(pyridin-2-yl)-1,2,4-thiadiazol-5-amines as Novel Macrofilaricidal Compounds for the Treatment of Human Filarial Infections.Journal of medicinal chemistry · 2022Article
- A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi.PLoS neglected tropical diseases · 2022Article
- A qPCR to quantify Wolbachia from few Onchocerca volvulus microfilariae as a surrogate for adult worm histology in clinical trials of antiwolbachial drugs.Parasitology research · 2022Article
- Current perspective of new anti-Wolbachial and direct-acting macrofilaricidal drugs as treatment strategies for human filariasis.GMS infectious diseases · 2022Review
- Human filariasis-contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model.Parasitology research · 2021Review
- Onchocerciasis drug development: from preclinical models to humans.Parasitology research · 2021Review
- Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration.PLoS pathogens · 2021Review
- Dual RNAseq analyses at soma and germline levels reveal evolutionary innovations in the elephantiasis-agent Brugia malayi, and adaptation of its Wolbachia endosymbionts.PLoS neglected tropical diseases · 2021Article
- Corallopyronin A for short-course anti-wolbachial, macrofilaricidal treatment of filarial infections.PLoS neglected tropical diseases · 2020Article
- The endosymbiont Wolbachia rebounds following antibiotic treatment.PLoS pathogens · 2020Article
- Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode Litomosoides sigmodontis in vivo and inhibits Onchocerca spec. motility in vitro.PLoS neglected tropical diseases · 2020Article
- Assembling Pharma Resources to Tackle Diseases of Underserved Populations.ACS medicinal chemistry letters · 2020Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depletion of Wolbachia endosymbionts of human pathogenic filariae using 4-6 weeks of doxycycline treatment can lead to permanent sterilization and adult filarial death. We investigated the anti-Wolbachia drug candidate ABBV-4083 in the Litomosoides sigmodontis rodent model to determine Wolbachia depletion kinetics with different regimens. Wolbachia reduction occurred in mice as early as 3 days after the initiation of ABBV-4083 treatment and continued throughout a 10-day treatment period. Importantly, Wolbachia levels continued to decline after a 5-day-treatment from 91.5% to 99.9% during a 3-week washout period. In jirds, two weeks of ABBV-4083 treatment (100mg/kg once-per-day) caused a >99.9% Wolbachia depletion in female adult worms, and the kinetics of Wolbachia depletion were recapitulated in peripheral blood microfilariae. Similar to Wolbachia depletion, inhibition of embryogenesis was time-dependent in ABBV-4083-treated jirds, leading to a complete lack of late embryonic stages (stretched microfilariae) and lack of peripheral microfilariae in 5/6 ABBV-4083-treated jirds by 14 weeks after treatment. Twice daily treatment in comparison to once daily treatment with ABBV-4083 did not significantly improve Wolbachia depletion. Moreover, up to 4 nonconsecutive daily treatments within a 14-dose regimen did not significantly erode Wolbachia depletion. Within the limitations of an animal model that does not fully recapitulate human filarial disease, our studies suggest that Wolbachia depletion should be assessed clinically no earlier than 3-4 weeks after the end of treatment, and that Wolbachia depletion in microfilariae may be a viable surrogate marker for the depletion within adult worms. Furthermore, strict daily adherence to the dosing regimen with anti-Wolbachia candidates may not be required, provided that the full regimen is subsequently completed.
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