Advances in the discovery and development of trematocidal drugs

Abstract

More than 10% of the world's population are at risk of schistosomiasis and food-borne trematodiasis and an estimated 250 million individuals are infected with the causative agents, namely trematode worms. Yet, schistosomiasis and food-borne trematodiasis are so-called neglected tropical diseases because they affect the poorest people of the world. There are only two drugs available for the treatment and control of schistosomiasis and food-borne trematodiasis, praziquantel and triclabendazole. Discovered in the 1970s and 1980s, these drugs show a good safety profile, are efficacious after administration of single oral doses and have become inexpensive. Because the neglected tropical diseases affect the global poor, there is little incentive for the Western pharmaceutical manufacturers to invest in the development of new trematocidal drugs. Fortunately, we are witnessing a sea change in the neglected tropical disease drug development landscape that should facilitate the discovery, development and deployment of new drugs. This review begins with the pressing need for novel treatment options for major trematode infections. The literature on possible drug targets is then summarised and recent advances in biological screening are put forward. The progress made in trematocidal drug development, particularly the artemisinins, is also reviewed. Finally, postmarketing issues of trematocidal drugs are discussed and the authors conclude that innovative environments for the discovery and development of novel trematocidal drugs have emerged.

Keywords::

• artemisinins
• drug development
• drug discovery
• food-borne trematodiasis
• peroxides
• praziquantel
• schistosomiasis
• synthetic trioxolanes
• triclabendazole

Acknowledgements

We thank S Nwaka from TDR for inviting us to prepare this review for a special issue of Expert Opinion on Drug Discovery. We thank M Tanner and R Brun from the Swiss Tropical Institute (Basel, Switzerland), SH Xiao from the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Shanghai, China) and JL Vennerstrom from the College of Pharmacy, University of Nebraska Medical Center (Nebraska, USA) for the many years of stimulating exchanges with an emphasis on drug discovery and development in our ‘wormy world’. We are grateful to the Swiss National Science Foundation for sustained financial support, via projects PMPDB-114358 (J. Keiser) and PPOOB-102883 (J. Utzinger).