Parasitic Helminths. Targets, Screens, Drugs and Vaccines (Drug Discovery in Infectious Diseases, Vol. 3)

Description

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.

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, RichardJ. 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

Authors

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 Tubingen, 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 Tubingen 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.