Roadmap for development of therapeutics for helminths

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

• Drug repurposing has acquired special relevance in several therapeutic fields. Could the use of old drugs for new indications be a valid strategy to be explored in resistant nematodes? The following specific questions should be used as a guide to assess the search for drug repurposing:
• Is it possible to find new anthelmintic indications for old available drugs?
• Could these potential new indications improve helminth/parasite control in practice?
• Could these potential new indications improve helminth/parasite control in practice in the context of anthelmintic resistance?
• Repurposing old medicines may include old drugs not originally intended for parasite control. Could they be used alone or in combination with existing anthelmintics?
• Can current drugs be used at higher doses, perhaps in combination to elicit other loci of activity not normally activated at normal therapeutic levels?

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

• Gathering information on new anthelmintic indications for old existing drugs.
• Further understanding of underlying mechanisms behind anthelmintic resistance.
• Efficiently screening libraries of old drugs against multiple species of parasites. (see Lead Summary 12)

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

Efficacy studies using old drugs with “potential anthelmintic activity” administered at different doses, co-administered, and administered against different stages of different helminth parasites.

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

Validated animal models involving different target and/or model parasites.

Existing knowledge including successes and failures

• High oxfendazole doses (30 mg/kg) demonstrated a high efficacy against Taenia solium cysticerci in pigs, and against adult liver flukes in pigs and sheep.
• High doses (x 10) of albendazole and ivermectin ´reverse´ resistance in H. contortus. Some of the available knowledge is encouraging regarding the potential of old existing drug (used under novel/alternative indications) to control helminth parasites.