Milestones of helmintic research at Bayer

Harder, Achim

doi:10.1007/s00436-001-0551-x

Cited by 15 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite these drawbacks, phenotypic screening has successfully identified PZQ and other vital anthelmintics (e.g., albendazole and ivermectin) that are in medical use today. Most often, the compounds originated in the animal health sector as part of its discovery programs to identify veterinary anti-parasitics [46],[47].…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

et al. 2009

View full text Add to dashboard Cite

BackgroundPraziquantel (PZQ) is the only widely available drug to treat schistosomiasis. Given the potential for drug resistance, it is prudent to search for novel therapeutics. Identification of anti-schistosomal chemicals has traditionally relied on phenotypic (whole organism) screening with adult worms in vitro and/or animal models of disease—tools that limit automation and throughput with modern microtiter plate-formatted compound libraries.MethodsA partially automated, three-component phenotypic screen workflow is presented that utilizes at its apex the schistosomular stage of the parasite adapted to a 96-well plate format with a throughput of 640 compounds per month. Hits that arise are subsequently screened in vitro against adult parasites and finally for efficacy in a murine model of disease. Two GO/NO GO criteria filters in the workflow prioritize hit compounds for tests in the animal disease model in accordance with a target drug profile that demands short-course oral therapy. The screen workflow was inaugurated with 2,160 chemically diverse natural and synthetic compounds, of which 821 are drugs already approved for human use. This affords a unique starting point to ‘reposition’ (re-profile) drugs as anti-schistosomals with potential savings in development timelines and costs.FindingsMultiple and dynamic phenotypes could be categorized for schistosomula and adults in vitro, and a diverse set of ‘hit’ drugs and chemistries were identified, including anti-schistosomals, anthelmintics, antibiotics, and neuromodulators. Of those hits prioritized for tests in the animal disease model, a number of leads were identified, one of which compares reasonably well with PZQ in significantly decreasing worm and egg burdens, and disease-associated pathology. Data arising from the three components of the screen are posted online as a community resource.ConclusionsTo accelerate the identification of novel anti-schistosomals, we have developed a partially automated screen workflow that interfaces schistosomula with microtiter plate-formatted compound libraries. The workflow has identified various compounds and drugs as hits in vitro and leads, with the prescribed oral efficacy, in vivo. Efforts to improve throughput, automation, and rigor of the screening workflow are ongoing.

show abstract

Section: Discussionmentioning

confidence: 99%

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Early studies showed the compound acted as an acetylcholine agonist [31]. The compound was not marketed as a veterinary product as the drug had to be given twice on two consecutive days, which was a great disadvantage in the face of other existing anthelmintics for companion animals [32]. As tribendimidine, a symmetrical diamidine derivative of amidantel, is marketed in China for STH [33] and being pursued for human use, amidantel was not considered as a candidate from our analysis.…”

Section: Resultsmentioning

confidence: 99%

Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases

et al. 2011

View full text Add to dashboard Cite

BackgroundFew drugs are available for soil-transmitted helminthiasis (STH); the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives.MethodologyWe searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI) statements, European Public Assessment Reports (EPAR) and published literature). Concomitantly, we developed a target product profile (TPP) against which the products were compared.Principal FindingsThe paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside) and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.Conclusions/SignificanceFew of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

show abstract

“…It developed a number of antiprotozoal drugs that are of considerable importance, including the suramin (Naganol) against African trypanosomiasis (discovered in 1924), the antimalarial drug chloroquine (in 1934 to 1937), and nifurtimox against Chagas disease (in 1972) [84]. Bayer-developed anthelmintics include antimosan against Schistosoma mansoni (in 1931), Miracil D (lucanthone) against some schistosomes (in 1940), and niclosamide (in 1953), which was used against tapeworms before the discovery of praziquantel [85]. Now, emodepside is the latest Bayer drug entering the field of tropical medicine.…”

Section: From Animal Health To Neglected Tropical Diseasesmentioning

confidence: 99%

Development of emodepside as a possible adulticidal treatment for human onchocerciasis—The fruit of a successful industrial–academic collaboration

et al. 2021

View full text Add to dashboard Cite

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Therefore, elimination programs need time frames of decades, well exceeding the life span of adult worms. The situation is worsened by decreased ivermectin efficacy after long-term therapy. To improve treatment options against onchocerciasis, a drug development candidate should ideally kill or irreversibly sterilize adult worms. Emodepside is a broad-spectrum anthelmintic used for the treatment of parasitic nematodes in cats and dogs (Profender and Procox). Our current knowledge of the pharmacology of emodepside is the result of more than 2 decades of intensive collaborative research between academia and the pharmaceutical industry. Emodepside has a novel mode of action with a broad spectrum of activity, including against extraintestinal nematode stages such as migrating larvae or macrofilariae. Therefore, emodepside is considered to be among the most promising candidates for evaluation as an adulticide treatment against onchocerciasis. Consequently, in 2014, Bayer and the Drugs for Neglected Diseases initiative (DNDi) started a collaboration to develop emodepside for the treatment of patients suffering from the disease. Macrofilaricidal activity has been demonstrated in various models, including Onchocerca ochengi in cattle, the parasite most closely related to O. volvulus. Emodepside has now successfully passed Phase I clinical trials, and a Phase II study is planned. This Bayer–DNDi partnership is an outstanding example of “One World Health,” in which experience gained in veterinary science and drug development is translated to human health and leads to improved tools to combat neglected tropical diseases (NTDs) and shorten development pathways and timelines in an otherwise neglected area.

show abstract

Milestones of helmintic research at Bayer

Cited by 15 publications

References 9 publications

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening

Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases

Development of emodepside as a possible adulticidal treatment for human onchocerciasis—The fruit of a successful industrial–academic collaboration

Contact Info

Product

Resources

About