Roadmap for development of therapeutics for helminths

What are we trying to achieve and why? What is the problem we are trying to solve?

• Replacing animals in helminth research will be quite difficult in the foreseeable future do the current state of knowledge and technologies. Consequently, approaches that can refine and reduce the use of animals is a more achievable goal in the near-term
• Replacing higher mammals with rodents will potentially both reduce and refine since rodents are highly inbred and thus there is less to animal-to-animal variability. High variability in animal testing is a problem because it demands the use of larger group sizes and therefore more animals.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Most helminth parasites are quite host-specific, making it difficult to develop rodent models for those parasites
• Rodent model systems will need to be developed and validated independently for each helminth species
• Development of standardized molecular markers that can differentiate between different strains of the same parasite species
• Make use of state-of-the-art statistical models that can increase the power of experiments to draw relevant biological conclusions using fewer animals

What approaches could/should be taken to address the research question?

• (Refine) Develop rodent models that can replace the use of higher mammals (e.g. dogs, cats, horses, ruminants)
• (Reduce and refine) Test multiple strains (such as drug-susceptible and drug-resistant) and species of parasites in a single animal and use molecular markers to determine species-specific and strain-specific efficacy.
• (Reduce) Use statistical models to improve the information that can be obtained from experiments using fewer animals

What else needs to be done before we can solve this need?

• Research into modifying and adapting important species of helminths to survive and develop in a rodent system. This type of research has had minimal funding in the past few decades.
• Genetics and genomics research to enable the development of reliable and biologically relevant molecular markers for species, strains within a species and resistance status for each important drug class.

Existing knowledge including successes and failures

• A gerbil and a rat model exists for testing drugs against Haemonchus contortus and Trichostrongylus spp.
• Diagnostic panels of microsatellite markers have been developed for several important helminth species; these can be used to differentiate between strains of the same species
• Molecular assays exist to detect and measure resistance to benzimidazole anthelmintics