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Huntington’s Disease

Pathogenic Mechanisms and Implications for Therapeutics

  • 1st Edition - February 7, 2024
  • Latest edition
  • Editors: X. William Yang, Myriam Heiman, Leslie M. Thompson
  • Language: English

Huntington's disease (HD) is one of the most common dominantly inherited neurodegenerative disorders, characterized by a clinical triad of movement disorder, cognitive deficits, an… Read more

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Description

Huntington's disease (HD) is one of the most common dominantly inherited neurodegenerative disorders, characterized by a clinical triad of movement disorder, cognitive deficits, and psychiatric symptoms. Huntington’s Disease: Pathogenic Mechanisms and Implications for Therapeutics reviews the most up-do-date content on HD pathogenic mechanisms and cutting-edge thinking on therapeutic strategies for HD. Chapters explore areas that include the clinical features and genetic studies of HD, the cellular and molecular biology of normal huntingtin, a range of HD models, the diverse pathogenic mechanisms linked to mutant huntingtin, new approaches to HD pathogenesis, as well as emerging preclinical therapeutic approaches and clinical programs in the field.

Key features

  • Reviews the clinical course and genetics of HD
  • Reviews the biology of human huntingtin and HD-relevant cell types
  • Reviews the wide range of pathobiology associated with mutant huntingtin
  • Reviews genetic studies of HD and how these studies are informing the development of new therapeutic approaches
  • Reviews new tools and model systems for basic and translational research in HD, including new human-derived model systems, as well as systems biology and artificial intelligence–driven approaches
  • Provides an overview of new therapeutic approaches and current clinical programs in HD

Readership

Researchers and trainees in the field Huntington’s disease and related neurodegenerative disorders; Clinicians or clinical trainees in Neurology; Industry sectors/pharmaceutical or biotech companies: scientists and R&D or clinical leaders in these companies who are developing novel therapies for HD and related neurodegenerative disorders

Table of contents

1. Huntington’s Disease: Clinical Features, Genetic Diagnosis, and Brain Imaging
Carlos Estevez-Fraga, Mitsuko Nakajima and Sarah J. Tabrizi

2. Revolutionizing Clinical Research and Communication in Huntington’s Disease: The Huntington’s Disease Integrated Staging System (HD-ISS)
Cristina Sampaio, Jeffrey D. Long, Alexandra Mansbach, Sarah J. Tabrizi, Emily C. Gantman

3. Huntington’s Disease Genetics: Implications for Pathogenesis
Marcy E. Macdonald, Jong-Min Lee and James F. Gusella

4. The Instability of the Huntington’s Disease CAG Repeat Mutation
Vanessa C. Wheeler, Joseph C. Stone, Thomas H. Massey and Ricardo Mouro Pinto

5. Mechanisms of Somatic CAG -Repeat Expansions in Huntington’s Disease
Amit L. Deshmukh, Terence Gall-Duncan and Christopher E. Pearson

6. RNA-Mediated Pathogenic Mechanisms in Huntington’s Disease
Gillian P. Bates, Sandra Fienko, Christian Landles and Aikaterini-Smaragdi Papadopoulou

7. Huntingtin Protein-protein Interactions: From Biology to Therapeutic Targets
Eduardo Silva Ramos, Todd M. Greco, Ileana M. Cristea and Erich E. Wanker

8. Repeat-Associated Non-AUG (RAN) Translation and Huntington’s Disease: Pathology, Mechanistic and Therapeutic Perspectives
Monica Banez-Coronel, John Douglas Cleary and Laura P.W. Ranum

9. Proteostasis Function and Dysfunction in Huntington’s Disease
Juliana Abramovich, Korbin Kleczko, Vincent Masto and Judith Frydman

10. Autophagy and Huntington’s Disease
Katherine R. Croce, Hilary Grosso Jasutkar and Ai Yamamoto

11. SUMO Modification in Huntington’s Disease: Unraveling Complex Mechanisms for Therapeutic Insights
Charlene Smith, Joan S. Steffan and Leslie M. Thompson

12. Selective Vulnerability in Huntington’s Disease: From Excitotoxicity, Mitochondrial
Dysfunction, and Transcription Dysregulation to Therapeutic Opportunity
Jacob S. Deyell, Ravinder Gulia and Albert R. La Spada

13. Pathophysiology of Synapses and Circuits in Huntington Disease
Marja D. Sepers, James Mackay and Lynn A. Raymond

14. The Role of Glial Pathology in Huntington’s Disease
Steven A. Goldman

15. Systems Biology Study of Huntington’s Disease
Leonardo E. Dionisio, Peter Langfelder, Jeffrey S. Aaronson, Jim Rosinski and X. William Yang

16. Unbiased Genome-Wide Approaches to Identify Vulnerability Factors in Huntington’s Disease
Suphinya Sathitloetsakun and Myriam Heiman

17. Striatal Neuronal Models of Huntington’s Disease Via Direct Conversion: Modeling Age-dependent Disease Phenotypes
Young Mi Oh, Seong Won Lee and Andrew S. Yoo

18. Genetic Mouse Models to Explore Huntington’s Disease Mechanisms and Therapeutic Strategies
Michelle Gray, Scott O. Zeitlin, Aida Moran-Reyna and Jeh-Ping Liu

19. Huntington’s Disease: From Large Animal Models to HD Gene Therapy
Sen Yan, Xiao-Jiang Li and Shihua Li

20. Deep Learning and Deep Phenotyping of HD iPSCs: Applications to Study Biology and Test Therapeutics
Steven Finkbeiner

21. The Promise of an Underappreciated Therapeutic Target: Sleep and Circadian Rhythm Dysfunction in Huntington’s Disease
Christopher S. Colwell, Weiyi Tan and A. Jennifer Morton

22. Huntingtin Lowering Therapeutics
Neil Aronin, Miguel E. Sena-Esteves, Anastasia Khvorova, Marian Difiglia and Michael Brodsky

23. Gene Editing for HD: Therapeutic Prospects
Richard Z. Chen and Thomas F. Vogt

24. Current Clinical Trials of New Therapeutic Agents for Huntington’s Disease
Blair R. Leavitt

Review quotes

"Written by prominent leaders in the field, this is not only a must-read for clinicians and researchers of Huntington's disease, but also a highly valuable reference for people in neurodegenerative diseases field in general. The authors did an amazing job, with breadth and depth, in covering a wide range of critical aspects including genetics, molecular and cellular mechanisms of pathogenesis, pathology, patient symptoms and animal model phenotypes, and clinical trials. The literatures covered in this book include historical milestone discoveries as well as the most updated advances in research and therapeutic development. It is truly an indispensable resource for us."— Chenjian Li, Research Fellow, Hoover Institution, Stanford University

Product details

  • Edition: 1
  • Latest edition
  • Published: February 22, 2024
  • Language: English

About the editors

XY

X. William Yang

Dr. X. William Yang completed his B.S./M.S. degrees in Molecular Biophysics & Biochemistry at Yale University in 1991. He obtained M.D./Ph.D. training at Rockefeller University (Ph.D., 1998) and Weill Medical College of Cornell University (M.D., 2000). He co-invented the technology to engineer Bacterial Artificial Chromosomes (BACs) and to generate BAC transgenic mice. His laboratory at UCLA (established in 2002) pioneered the use of a BAC transgenic approach in mice to study pathogenesis of neurodegenerative disorders including Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease. The Yang lab has also applied novel genetic and systems biology approaches to study molecular networks in healthy and disease brains, and to study brain-wide morphology of genetically-defined neurons. He is a recipient of BRAIN Initiative Awards from NIH, Brain Disorder Award from McKnight Foundation, the Leslie Gehry Brenner Prize for Innovation in Science in 2014, and is an elected member of the American Society for Clinical Investigation.

Affiliations and expertise
University of California, Los Angeles

MH

Myriam Heiman

Myriam Heiman and her lab use HD patient tissue, as well as mouse and cell models of HD to understand why some cells are more or less vulnerable to the mutant HD gene, and use knowledge of these intrinsic differences to identify new therapeutic targets for HD. Dr. Heiman has pioneered the use of in vivo genetic screening in the mammalian brain, as well as the use of novel single-cell and cell type-specific transcriptional profiling tools to study HD. Her work has recently pointed to the importance of neuronal innate immune activation and cell type-specific mitochondrial dysfunction in HD pathogenesis. Myriam is the recipient of several awards, including an Early Career Investigators Innovation Award from the Bumpus Foundation and a EUREKA grant from the National Institutes of Health.
Affiliations and expertise
Picower Institute for Learning and Memory

LT

Leslie M. Thompson

Dr. Thompson is a Donald Bren and Chancellor’s Professor in the Departments of Psychiatry and Human Behavior and Neurobiology and Behavior at the University of California Irvine. She has studied Huntington’s disease (HD) for most of her scientific career and was a member of the international consortium that identified the causative gene for HD in 1993. Since that time, the Thompson laboratory has been actively engaged in investigating the fundamental molecular and cellular events that underlie how the mutant HD gene causes degeneration of specific brain cell populations to induce motor and cognitive decline and premature death of patients with the ultimate goal to develop new treatments, including stem-cell based treatments. Dr. Thompson is the recipient of several awards including the HDF Lesley Gehry Brenner Award for Scientific Innovation in 2013, an NIH Research Program R35 Award and was elected an AAAS fellow in 2013.

Affiliations and expertise
University of California, Irvine

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