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Parasitic Helminths: Targets, Screens, Drugs and Vaccines

Conor R. Caffrey (Editor), Paul M. Selzer (Series Editor)
ISBN: 978-3-527-33059-1
540 pages
August 2012, Wiley-Blackwell
Parasitic Helminths: Targets, Screens, Drugs and Vaccines (3527330593) cover image


This third volume in the successful 'Drug Discovery in Infectious Diseases' series is the first to deal with drug discovery in helminthic infections in human and animals. The result is a broad overview of different drug target evaluation methods, including specific examples of successful drug development against helminthes, and with a whole section devoted to vaccine development.
With its well-balanced mix of high-profile contributors from academia and industry, this handbook and reference will appeal to a wide audience, including parasitologists, pharmaceutical industry, epidemiologists, and veterinary scientists.
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Table of Contents

Foreword to Parasitic Helminths: Targets, Screens, Drugs and Vaccines V

Preface XI

List of Contributors XIII

Part One Targets 1

1 Ligand-Gated Ion Channels as Targets for Anthelmintic Drugs: Past, Current, and Future Perspectives 3
Kristin Lees, Ann Sluder, Niroda Shannan, Lance Hammerland, and David Sattelle

2 How Relevant is Caenorhabditis elegans as a Model for the Analysis of Parasitic Nematode Biology? 23
Lindy Holden-Dye and Robert J. Walker

3 Integrating and Mining Helminth Genomes to Discover and Prioritize Novel Therapeutic Targets 43
Dhanasekaran Shanmugam, Stuart A. Ralph, Santiago J. Carmona, Gregory J. Crowther, David S. Roos, and Fernán Agüero

4 Recent Progress in Transcriptomics of Key Gastrointestinal Nematodes of Animals – Fundamental Research Toward New Intervention Strategies 61
Cinzia Cantacessi, Bronwyn E. Campbell, Aaron R. Jex, Ross S. Hall, Neil D. Young, Matthew J. Nolan, and Robin B. Gasser

5 Harnessing Genomic Technologies to Explore the Molecular Biology of Liver Flukes-Major Implications for Fundamental and Applied Research 73
Neil D. Young, Aaron R. Jex, Cinzia Cantacessi, Bronwyn E. Campbell, and Robin B. Gasser

6 RNA Interference: A Potential Discovery Tool for Therapeutic Targets of Parasitic Nematodes 89
Collette Britton

7 RNA Interference as a Tool for Drug Discovery in Parasitic Flatworms 105
Akram A. Da.dara and Patrick J. Skelly

Part Two Screens 121

8 Mechanism-Based Screening Strategies for Anthelmintic Discovery 123
Timothy G. Geary

9 Identification and Profiling of Nematicidal Compounds in Veterinary Parasitology 135
Andreas Rohwer, Jürgen Lutz, Christophe Chassaing, Manfred Uphoff, Anja R. Heckeroth, and Paul M. Selzer

10 Quantitative High-Content Screening-Based Drug Discovery against Helmintic Diseases 159
Rahul Singh

11 Use of Rodent Models in the Discovery of Novel Anthelmintics 181
Rebecca Fankhauser, Linsey R. Cozzie, Bakela Nare, Kerrie Powell, Ann E. Sluder, and Lance G. Hammerland

12 To Kill a Mocking Worm: Strategies to Improve Caenorhabditis elegans as a Model System for use in Anthelmintic Discovery 201
Andrew R. Burns and Peter J. Roy

Part Three Drugs 217

13 Anthelmintic Drugs: Tools and Shortcuts for the Long Road from Discovery to Product 219
Eugenio L. de Hostos and Tue Nguyen

14 Antinematodal Drugs – Modes of Action and Resistance: And Worms Will Not Come to Thee (Shakespeare: Cymbeline: IV, ii) 233
Alan P. Robertson, Samuel K. Buxton, Sreekanth Puttachary, Sally M. Williamson, Adrian J. Wolstenholme, Cedric Neveu, Jacques Cabaret, Claude L. Charvet, and Richard J. Martin

15 Drugs and Targets to Perturb the Symbiosis of Wolbachia and Filarial Nematodes 251
Mark J. Taylor, Louise Ford, Achim Hoerauf, Ken Pfarr, Jeremy M. Foster, Sanjay Kumar, and Barton E. Slatko

16 Promise of Bacillus thuringiensis Crystal Proteins as Anthelmintics 267
Yan Hu and Raffi V. Aroian

17 Monepantel: From Discovery to Mode of Action 283
Ronald Kaminsky and Lucien Rufener

18 Discovery, Mode of Action, and Commercialization of Derquantel 297
Debra J. Woods, Steven J. Maeder, Alan P. Robertson, Richard J. Martin, Timothy G. Geary, David P. Thompson, Sandra S. Johnson, and George A. Conder

19 Praziquantel: Too Good to be Replaced? 309
Livia Pica-Mattoccia and Donato Cioli

20 Drug Discovery for Trematodiases: Challenges and Progress 323
Conor R. Caffrey, Jürg Utzinger, and Jennifer Keiser

Part Four Vaccines 341

21 Barefoot thru. the Valley of Darkness: Preclinical Development of a Human Hookworm Vaccine 343
Jeffrey M. Bethony, Maria Victoria Periago, and Amar R. Jariwala

22 Vaccines Linked to Chemotherapy: A New Approach to Control Helminth Infections 357
Sara Lustigman, James H. McKerrow, and Maria Elena Bottazzi

23 Antifilarial Vaccine Development: Present and Future Approaches 377
Sara Lustigman, David Abraham, and Thomas R. Klei

24 Proteases as Vaccines Against Gastrointestinal Nematode Parasites of Sheep and Cattle 399
David Knox

25 Schistosomiasis Vaccines – New Approaches to Antigen Discovery and Promising New Candidates 421
Alex Loukas, Soraya Gaze, Mark Pearson, Denise Doolan, Philip Felgner, David Diemert, Donald P. McManus, Patrick Driguez, and Jeffrey Bethony

26 Sm14 Schistosoma mansoni Fatty Acid-Binding Protein: Molecular Basis for an Antihelminth Vaccine 435
Miriam Tendler, Celso Raul Romero Ramos, and Andrew J.G. Simpson

27 Mechanisms of Immune Modulation by Fasciola hepatica: Importance for Vaccine Development and for Novel Immunotherapeutics 451
Mark W. Robinson, John P. Dalton, Sandra M. O.Neill, and Sheila M. Donnelly

28 Prospects for Immunoprophylaxis Against Fasciola hepatica (Liver Fluke) 465
Terry W. Spithill, Carlos Carmona, David Piedrafita, and Peter M. Smooker

29 Vaccines Against Cestode Parasites 485
Marshall W. Lightowlers, Charles G. Gauci, Abdul Jabbar, and Cristian Alvarez

Index 505

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Author Information

Volume editor:
Conor R. Caffrey completed his Ph.D. thesis research in 1993 at University College Dublin. He then moved to the Department of Tropical Medicine and Hygiene at the University of Heidelberg as a Wellcome Trust Travelling Research Scholar. Between 1998 and 2000, he was a post-doctoral scholar at the Department of Pathology of the University of California San Francisco. After a brief faculty appointment at the University of Wales, Aberystwyth, Dr. Caffrey returned to UCSF in 2001 to direct the Biochemistry and Molecular Parasitology Core of the Sandler Center the Sandler Center for Basic Research in Parasitic Diseases (now the Sandler Center for Drug Discovery). Dr. Caffrey?s current research focus is pre-clinical drug discovery for tropical infectious diseases, particularly schistosomiasis and African trypanosomiasis.

Series Editor:
Prof. Dr. Paul M. Selzer studied Biology, Parasitology, and Biochemistry at the University of Tübingen, Germany, where he also received his PhD in Biochemistry on subjects related to the protozoan parasite Trypanosoma brucei. As a post-doctoral fellow he spent three years in the parasitology and tropical disease laboratory of Prof. James H. McKerrow at the University of California, San Francisco (UCSF). Within the Molecular Design Institute at UCSF Dr. Selzer was introduced to modern drug discovery approaches and technologies. He broadened his scientific and business knowledge as a researcher within diverse pharmaceutical companies including Boehringer Mannheim GmbH, Germany, SmithKline Beecham p.l.c., UK, Hoechst Roussel Vet GmbH, Germany, and finally Intervet Innovation GmbH, Germany, a part of Intervet/Schering-Plough Animal Health. Dr. Selzer is also a teacher in Biochemistry, Bioinformatics, and Chemoinformatics at the University of Tübingen in the Department of Biochemistry, which awarded him the title of Professor for his achievements in teaching and research. In 2008, he was also awarded an Honorary Professorship in the Department of Infection and Immunity at the University of Glasgow, UK.
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“This book clearly demonstrates the need of a more unified scientific community for developing successful strategies, by working together and building a strong network of active cooperations with complementary expertise between academic and industry consortia. It will be particularly true for the success of anthelmintic drug and vaccine discovery programs.”  (ChemMedChem, 1 January 2013)


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