Roadmap for development of therapeutics for helminths

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

Identify new protein targets for anthelmintic drug development

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

• Knowledge of the genomics, transcriptomics, and general physiology of helminths is still rather poor; 40% of more of nematode genes have unknown function
• We still lack knowledge of the full spectrum of targets of currently used anthelmintics; evidence suggests these drugs may be targeting more loci than is currently known.
• If current drugs are highly effective because they target multiple loci in worms, then identifying individual targets may turn out to be a failed approach. It is noteworthy that all anthelmintics to date were discovered using organismaltesting and no target-based drugs have yet been developed despite more than two decades of effort.

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

• Improve knowledge of how current anthelmintics work by identifying all loci where they have activity and/or where changes in specific loci cause resistance to the drug
• Improve knowledge of the genomics, transcriptomics, and general physiology of helminths
• Appreciate that single target drugs may fail to be sufficiently effective by themselves, but might be effective in a cocktail of several drugs each targeting a different loci.

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

• Currently available technologies should be sufficient to solve this need. The need will be for sufficient funding to support the necessary research efforts.
• Strong target/compound leads will be pursued by individual companies who will not want to share their intellectual property. However, those leads may fail as independent targets/compounds. Thus a system or consortium should be put into place where multiple leads from several companies that fail as a stand-alone product can be investigated together for the potential to develop a cocktail of compounds that may yield an effective product.

Existing knowledge including successes and failures

• Despite more than two decades of research, no anthelmintics using a targeted approach have been developed.
• This failure should lead to questions about the validity of this approach, however, as knowledge and tools continue to improve, success is still possible. Additionally, a cocktail of compounds discovered using a target-based approach might be highly effective.