Ectoparasites Drug Discovery Against Moving Targets

This first book specifically dedicated to ectoparasite drug discovery is unique in providing insights from the veterinary as well as the medical perspective, covering research from both industry and academia while paving the way for new synergies between the two research communities.
Edited by a team combining 80 years of experience in academic research and industrial antiparasitic drug discovery, this volume of Drug Discovery in Infectious Diseases summarizes current knowledge in this rapidly expanding field. Comprehensive yet concise, this ready reference blends solid background information on ectoparasite biology with the very latest methods in ectoparasite drug discovery. Three major parts cover current ectoparasite control strategies and the threat of drug resistance, screening and drug evaluation, and the new isoxazoline class of ectoparasiticides. The future potential of mechanism-based approaches for repellents and parasiticides is thoroughly discussed, as are strategies for vaccines against ectoparasites, making the book ideal for parasitologists in academia as well as researchers working in the pharmaceutical industry.

Dr. Charles Q. Meng earned his PhD degree in Organic Chemistry from the University of Zurich in 1991. Upon completing postdoctoral research at Roche (Basel) and the University of Montreal he worked for Allelix Biopharmaceuticals (Mississauga, Ontario) on migraine drug discovery and AtheroGenics (Alpharetta, Georgia) on cardiovascular drug discovery. In 2007 Dr. Meng joined the pharmaceutical discovery and research group of Merial, a Sanofi company then and part of Boehringer Ingelheim now, focusing on antiparasitic drug discovery for animal health. He is an inventor of 25 issued US patents and an author of over 30 publications of original research, reviews, commentaries and book chapters.

Dr. Ann E. Sluder earned a PhD in Biochemistry from Duke University in 1988 studying transcription biochemistry in Drosophila melanogaster. During postdoctoral studies at Harvard Medical School and Massachusetts General Hospital she initiated a research program focused on nuclear receptor transcription factors in the nematode Caenorhabditis elegans, which she expanded to include parasitic nematodes while an Assistant Professor of Cellular Biology at the University of Georgia. From 2000-2014 Dr. Sluder worked in drug discovery for antiparasitics, orphan neuromuscular diseases and viral and fungal infections at two biotechnology companies. In 2015 she joined the Vaccine and Immunotherapy Center of the Massachusetts General Hospital, managing preclinical development programs in infectious diseases, cancer, and diabetes.

Prof. Dr. Paul M. Selzer studied Biology, Parasitology, and Biochemistry at the University of Tübingen, Germany, where he also received his PhD in Biochemistry. He spent three years at the Molecular Design Institute and the Tropical Disease Research Laboratory at the University of California, San Francisco. During his career he has worked as a researcher and scientific manager for several pharmaceutical companies, and is currently holding a management position in antiparasitic drug discovery at Boehringer Ingelheim Animal Health. He is also a visiting professor at the Interfaculty Institute of Biochemistry of the University of Tübingen, DE and an honorary professor of the Department of Infection, Immunity, and Inflammation at the University of Glasgow, UK.

List of Contributors VII

Foreword XIII

Preface XV

Part One Strategies & Resistance 1

1 Comparison of Anti‐ectoparasite and Anti‐endoparasite Therapies and Control Strategies 3
Debra J. Woods*, Tom L. McTier, and Andrew A. DeRosa

2 vaccination Against Ticks 25
Theo P.M. Schetters*

3 Blocking Transmission of vector‐borne Diseases  43
Sandra Schorderet‐Weber, Sandra Noack, Paul M. Selzer, and Ronald Kaminsky*

4 The Threat and Reality of Drug Resistance in the Cattle Tick Rhipicephalus (Boophilus) microplus  95
Heinz Sager*, Léonore Lovis, Christian Epe, and Ronald Kaminsky

5 Monitoring Drug Sensitivity in Cattle Ticks 109
Leonore Lovis, Christian Epe, Ronald Kaminsky, and Heinz Sager*

6 New Developments in the Control of Human Lice 119
John M. Clark*

Part Two Screens & Models 139

7 Molecular Targets to Impair Blood Meal Processing in Ticks 141
Petr Kopáček*, Jan Perner, Daniel Sojka, Radek Šíma, and Ondřej Hajdušek

8 Whole‐organism Screens for Ectoparasites 167
Jeffrey N. Clark* and Cedric J. Pearce

9 In vitro Feeding Methods for Hematophagous Arthropods and Their Application in Drug Discovery 187
Ard M. Nijhof* and Katharine R. Tyson

10 Testing in Laboratory Animal Models for Ectoparasiticide Discovery and Development 205
Sandra Schorderet‐Weber* and Ronald Kaminsky

11 Testing in Target Hosts for Ectoparasiticide Discovery and Development 223
Jeffrey N. Clark*

Part Three Isoxazolines 243

12 Isoxazolines: A Novel Chemotype Highly Effective on Ectoparasites 245
Tina Weber and Paul M. Selzer*

13 The Discovery of Afoxolaner: A New Ectoparasiticide for Dogs  259
Ming Xu, Jeffrey K. Long, George P. Lahm*, Wesley L. Shoop, Daniel Cordova, Ty Wagerle, Ben K. Smith, Thomas F. Pahutski, Rafael Shapiro, Michael Mahaffey, Eric J. Hartline, Brandon R. Gould, Molly E. Waddell, Richard G. McDowell, John B. Kinney, Gail S. Jones, Robert F. Dietrich, Mark E. Schroeder, Daniel F. Rhoades, Eric A. Benner, and Pat N. Confalone

14 Development of Afoxolaner as a New Ectoparasiticide for Dogs 273
Laura Letendre*, Diane Larsen, and Mark Soll

15 Discovery, Development, and Commercialization of Sarolaner (Simparica^®), A Novel Oral Isoxazoline Ectoparasiticide for Dogs 295
Debra J. Woods* and Tom L. McTier

16 Isoxazolines: Preeminent Ectoparasiticides of the Early Twenty‐first Century 319
Alan Long*

Index 353