Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections

Abstract

Background Helminthiases are very prevalent worldwide, yet their treatment and control rely on a handful of drugs. Emodepside, a marketed broad-spectrum veterinary anthelminthic with a unique mechanism of action, undergoing development for onchocerciasis is an interesting anthelmintic drug candidate. We tested the in vitro and in vivo activity of emodepside on nematode species that serve as models for human soil-transmitted helminth infection as well as on schistosomes. Methods In vitro viability assays were performed over a time course of 72 hours for Trichuris muris , Necator americanus , Ancylostoma ceylanicum , Heligmosomoides polygyrus , Strongyloides ratti , Schistosoma mansoni and Schistosoma haematobium . The drug effect was determined by the survival rate for the larvae and by phenotypical scores for the adult worms. Additionally, mice infected with T. muris and hamsters harboring hookworm infection ( N. americanus or A. ceylanicum ) were administered orally with emodepside at doses ranging from 1.25 to 75 mg/kg. Expelled worms in the feces were counted until 3 days post-drug intake and worms residing in the intestines were collected and counted after dissection. Results After 24 hours, emodepside was very active in vitro against both larval and adult stages of the nematodes T. muris , A. ceylanicum , N. americanus , H. polygyrus and S. ratti (IC 50 < 4 µM). The good in vitro activity was confirmed in vivo . Hamsters infected with the hookworms were cured when administered orally with 2.5 mg/kg of the drug. Emodepside was also highly active in vivo against T. muris (ED 50 = 1.2 mg/kg). Emodepside was moderately active on schistosomula in vitro (IC 50 < 8 µM) 24 h post-drug incubation and its activity on adult S. mansoni and S. haematobium was low (IC 50 : 30–50 µM). Conclusions Emodepside is highly active against a broad range of nematode species both in vitro and in vivo . The development of emodepside for treating soil-transmitted helminth infections should be pursued. Electronic supplementary material The online version of this article...

The narrow-spectrum anthelmintic oxantel is a potent agonist of a novel acetylcholine receptor subtype in whipworms

“…Emodepside has recently shown promising results when tested in vitro on T . muris , and the hookworms Ancylostoma ceylanicum , Necator americanus , and in vivo in animal models infected with the above mentioned parasitic species [ 69 ]. Thus, emodepside is a promising drug candidate for the treatment of not only trichuriasis, but for STHs.…”

Adverse Drug Reactions After Administration of Emodepside/Praziquantel (Profender®) in an MDR1-Mutant Australian Shepherd Dog: Case Report

“…However, adverse reactions of the Australian Shepherd in the current case were serious and very distressing to both animal and owner, in a way that was not expected from the SPC statement. This is particularly significant, since there is no antidote or treatment option established so far (4, 5, 32). Diazepam and further benzodiazepines, as well as barbiturates, are often used to treat generalized tremor, but showed limited improvement in the present case as well as in former cases (14).…”

Where are all the anthelmintics? Challenges and opportunities on the path to new anthelmintics

“…However, due to the significant costs of developing human anthelmintic medicines, subsequent research has been driven by veterinary commercial needs and the majority of human anthelmintics have been leveraged from AH pharmaceutical research ( Aziz et al, 1982 ; Woods et al, 2007 ; Kyne et al, 2019 ). Ongoing collaborations between industry and academia continue to tackle human helminth infections with existing animal anthelmintics, including the companion animal anthelmintic, emodepside, which is currently being evaluated for onchocerciasis in humans ( Karpstein et al, 2019 ).…”