Roadmap for development of therapeutics for helminths

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

• There are increasing societal pressures to reduce and replace the use of animals in research
• Reducing and/or replacing the use of animals in research will require the development of alternative approaches that can replicate the complex host and the host-parasite dynamics that defines the pharmacokinetics and pharmacodynamics of a drug when administered to a animal.
• Ex vivo and in vitro alternatives to the use of animals needs to provide equivalent, or at least translatable data for efficacy, safety, etc.

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

• The adult stages and many of the larval stages of helminth parasites live inside of animals, and cannot survive and develop outside of the animal host
• For the most part, we lack the knowledge necessary to replicate the host milieu in an ex vivo or in vitro environment
• Advances in the methods and procedures for the ex vivo or in vitro culturing of parasitic stages of helminths are needed

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

• Studies investigating novel approaches for replicating the host environment in an ex vivo or in vitro system are needed
• Improved knowledge of host-parasite dynamic can enable the development and use of in silico experiments, that can be used to test relevant aspects of multiple different dosing regimes

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

• Additional knowledge of helminth physiology and on the role of host proteins, miRNAs, lectins, and other host signals in creating an environment conducive to the parasite’s survival
• In addition to knowledge of general mechanisms, host-parasite-specific mechanisms will also need to be understood.

Existing knowledge including successes and failures

• Several protocols for culturing parasitic stages of helminths exist; however, they only allow for short-term survival
• It is still not possible to successfully complete the life cycle of a helminth parasite outside of a host animal.