Roadmap for development of therapeutics for helminths

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

• Search for approaches to achieve improved therapeutic response for existing anthelmintics in livestock animalsin situations where their use is still valid (i.e. some drug susceptible cattle nematodes).
• Identification of novel active pharmaceutical and/or phytochemicalingredients (API) with alternative mode of action and/or expanded therapeutic response against helminth parasites resistant to other available anthelmintic drugs.

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

• Considering the increasing concern regarding the development of drug resistance, the use of pharmacology-based information is critical to design successful strategies for future helminth parasite control in livestock.
• Integrated pharmacokinetic/pharmacodynamic and clinical pharmaco-parasitology knowledge are required to identify, characterize and preserve novel anthelmintic compounds.
• To implement phenotypic and/or mechanisms-based target identification programs to come up with novel API with alternative mode of anthelmintic action
• To extend the lifespan (preserve) of the novel API with alternative modes of action
• To provide alternative parasite control measures (i.e. bioactive phytochemicals, vaccines, etc) that can be jointly/complementary used with novel API in the field in the short time.

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

• A sustained and robust pipeline of new anthelmintic active compounds is critical to preserve the efficiency of intensive livestock production.
• Large scale screening technologies to identify novel chemicals active against R nematodes
• Genomic-assisted anthelmintic drug discovery programs
• Integrated basic and applied pharmaco-parasitological research with reasonable funding support.

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

• Improved molecular understanding of the mechanisms of drug resistance in helminth parasites.
• Improved diagnosis with genetic markers of drug resistance available for field use.
• Further interaction among academia, pharmaceutical industry and regulatory bodies.
• Greater knowledge of parasite genomics and transcriptonomics in order to identify new drug targets
• Greater knowledge of critical parasite-specific biochemical pathways that can be targeted with drugs

Existing knowledge including successes and failures

Different pharmacokinetic-based approaches to enhance parasite exposure (pharmacokinetic optimisation) and the use of a mixture of molecules from different chemical families (drug combinations) have been assessed as valid strategies to control resistant parasites and to slow the selection for further resistance. These experimentally successful strategies need to be further validated in field conditions.