Mechanism-based screening: discovery of the next generation of anthelmintics depends upon more basic research

The therapeutic arsenal for the control of helminth infections contains onl y a few chemical classes. The development and spread of resistance has erod ed the utility of most currently available anthelmintics, at least for some indications, and is a constant threat to further reduce the options for tr eatment. Discovery and development of novel anthelmintic templates is strat egically necessary to preserve the economic and health advantages now gaine d through chemotherapy. As the costs of development escalate, the question of how best to discover new drugs becomes paramount. Although random screen ing in infected animals led to the discovery of all currently available ant helmintics, cost constraints and a perception of diminishing returns requir e new approaches. Taking a cue from drug discovery programmes for human ill nesses, we suggest that mechanism-based screening will provide the next gen eration of anthelmintic molecules. Critical to success in this venture will be the exploitation of the Caenorhabditis elegans genome through bioinform atics and genetic technologies. The greatest obstacle to success in this en deavour is the paucity of information available about the molecular physiol ogy of helminths, making the choice of a discovery target a risky propositi on. (C) 1998 Australian Society for Parasitology. Published by Elsevier Sci ence Ltd. All rights reserved.