Conor R Caffrey1, W Evan Secor. 1. Sandler Center for Drug Discovery, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, California 94158, USA. conor.caffrey@ucsf.edu
Abstract
PURPOSE OF REVIEW: Schistosomiasis is a chronic and morbid disease that affects hundreds of millions of the poorest individuals in (sub)tropical regions, particularly sub-Saharan Africa. Just one drug, praziquantel (PZQ), is available. As discussed, efforts to expand mass drug administration programs may accelerate the emergence of resistance. In addition, PZQ's peculiar pharmacological profile and undefined mechanism of action(s) complicate discriminating incomplete efficacy from true resistance. Accordingly, and in spite of the challenges associated with developing new antischistosomals as discussed herein, alternatives to PZQ should be identified. Various strategies to do this are highlighted here. RECENT FINDINGS: The last 2 years have witnessed more engagement of the necessary infrastructure combined with the application of the latest strategies and technologies to facilitate antischistosomal drug discovery. Preclinical and clinical evaluation of new chemistries has benefited from various consortia and institutions that underwrite drug development for antiparasitics in general. Drug repositioning, target-based drug design, improved automation for compound screening, genomics and functional genomics are just some of the tools now being applied to identify possible new drugs and drug targets. SUMMARY: The new momentum toward the discovery of alternatives to PZQ is encouraging but needs to be sustained by a stronger advocacy for drug development, in addition to drug deployment.
PURPOSE OF REVIEW: Schistosomiasis is a chronic and morbid disease that affects hundreds of millions of the poorest individuals in (sub)tropical regions, particularly sub-Saharan Africa. Just one drug, praziquantel (PZQ), is available. As discussed, efforts to expand mass drug administration programs may accelerate the emergence of resistance. In addition, PZQ's peculiar pharmacological profile and undefined mechanism of action(s) complicate discriminating incomplete efficacy from true resistance. Accordingly, and in spite of the challenges associated with developing new antischistosomals as discussed herein, alternatives to PZQ should be identified. Various strategies to do this are highlighted here. RECENT FINDINGS: The last 2 years have witnessed more engagement of the necessary infrastructure combined with the application of the latest strategies and technologies to facilitate antischistosomal drug discovery. Preclinical and clinical evaluation of new chemistries has benefited from various consortia and institutions that underwrite drug development for antiparasitics in general. Drug repositioning, target-based drug design, improved automation for compound screening, genomics and functional genomics are just some of the tools now being applied to identify possible new drugs and drug targets. SUMMARY: The new momentum toward the discovery of alternatives to PZQ is encouraging but needs to be sustained by a stronger advocacy for drug development, in addition to drug deployment.
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