Parkinsons Disease Animal Models Current Therapies And Clinical Trials

Despite being described about 200 years ago, the pathophysiology of Parkinson’s disease (PD) is not well understood due to its complex etiology and heterogeneity of symptoms and progression. Animal models provide a great opportunity to follow the progression of neurodegeneration and to screen potent therapeutic molecules, knowledge of which can be critical for different levels of clinical trials. Contemporary health technologies are coming in handy to accelerate the pace of developing novel and refined therapeutic strategies for PD. This book, Parkinson’s Disease - Animal Models, Current Therapies and Clinical Trials, provides a comprehensive overview of PD, presenting information on animal models of PD and contemporary therapeutic strategies, health technologies, clinical trials, and their influence on the quality of life of patients with PD.

This second volume follows on from Part I by reviewing the variety of animal models of PD current available (from drosophila to rodents to non-human primate species) and their specific contributions to PD research. This is followed by comprehensive coverage of functional neuroimaging studies that explore different pathophysiological questions and evaluate treatment outcome in PD patients. Different areas of experimental therapeutics and outstanding challenges to PD treatment are presented in a concluding group of articles. Complete overview of hot topics and approaches to current PD research, from molecules, to brain circuits, to clinical and therapeutic applications Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist

Nervous system diseases and disorders are highly prevalent and substantially contribute to the overall disease burden. Despite significant information provided by the use of animal models in the understanding of the biology of nervous system disorders and the development of therapeutics; limitations have also been identified. Treatment options that are high in efficacy and low in side effects are still lacking for many diseases and, in some cases are nonexistent. A particular problem in drug development is the high rate of attrition in Phase II and III clinical trials. Why do many therapeutics show promise in preclinical animal models but then fail to elicit predicted effects when tested in humans? On March 28 and 29, 2012, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders convened the workshop "Improving Translation of Animal Models for Nervous System Disorders" to discuss potential opportunities for maximizing the translation of new therapies from animal models to clinical practice. The primary focus of the workshop was to examine mechanisms for increasing the efficiency of translational neuroscience research through discussions about how and when to use animal models most effectively and then best approaches for the interpretation of the data collected. Specifically, the workshop objectives were to: discuss key issues that contribute to poor translation of animal models in nervous system disorders, examine case studies that highlight successes and failures in the development and application of animal models, consider strategies to increase the scientific rigor of preclinical efficacy testing, explore the benefits and challenges to developing standardized animal and behavioral models. Improving the Utility and Translation of Animal Models for Nervous System Disorders: Workshop Summary also identifies methods to facilitate development of corresponding animal and clinical endpoints, indentifies methods that would maximize bidirectional translation between basic and clinical research and determines the next steps that will be critical for improvement of the development and testing of animal models of disorders of the nervous system.

Parkinson's disease (PD) is characterised clinically by various non-motor and progressive motor symptoms, pathologically by loss of dopamine producing cells and intraneuronal cytoplasmic inclusions composed primarily of ?-synuclein. By the time a patient first presents with symptoms of Parkinson's disease at the clinic, a significant proportion of the cells in the substantia nigra have already been destroyed. This degeneration progresses despite the current therapies until the cell loss is so great that the quality of normal life is compromised. The dopamine precursor levodopa is the most valuable drug currently available for the treatment of PD. However for most PD patients, the optimal clinical benefit from levodopa decreases around five to six years of treatment. The aim of the chapters of this book is to work towards an understanding in the mechanisms of degeneration and to develop disease modifying therapies.

Recent Advances in Parkinson ́s Disease Research, Volume 252, represents a follow-up on two previous volumes presented in the Progress in Brain Research series, Volumes 193 and 193, both published in 2010. It contains a collection of overview articles written by leading researchers in Parkinson's, discussing the most important advances made in basic, translational and clinical research. Topics of note in this new release include What can we learn from iPS cell models of PD, What can we learn from animal models of PD?, Molecular basis of selective neuronal vulnerability in PD, Role of innate and adaptive immunity in Parkinson ́s disease, and much more. Covers all key aspects of current research on Parkinson ́s disease Includes topics that range from basic studies on disease models and pathogenic pathways (e.g., protein misfolding, immune and glial mechanisms) to clinical studies on disease features, microbiome, pathophysiology and therapeutic approaches Presents articles authored by world leaders in their respective fields

Neurological Disorders is written for researchers in both academia and the pharmaceutical industry who use animal models in research and development of drugs for neurological disorders such as neurofibromatosis, Alzheimer’s disease, Parkinson’s disease, Huntington disease, ALS, and the epilepsies. Neurological Disorders has introductory chapters expressing the view of the role and relevance of animal models for drug discovery and development for the treatment of psychiatric disorders from the perspective of (a) academic basic neuroscientific research, (b) applied pharmaceutical drug discovery and development, and (c) issues of clinical trial design and regulatory agencies limitations. Each volume examines the rationale, use, robustness and limitations of animal models in each therapeutic area covered and discuss the use of animal models for target identification and validation. The clinical relevance of animal models is discussed in terms of major limitations in cross-species comparisons, clinical trial design of drug candidates, and how clinical trial endpoints could be improved. The aim of this series of volumes on Animal and Translational Models for CNS Drug Discovery is to identify and provide common endpoints between species that can serve to inform both the clinic and the bench with the information needed to accelerate clinically-effective CNS drug discovery. This is the second volume in the three volume-set, Animal and Translational Models for CNS Drug Discovery 978-0-12-373861-5, which is also available for purchase individually. Clinical, academic, government and industry perspectives fostering integrated communication between principle participants at all stages of the drug discovery process Critical evaluation of animal and translational models improving transition from drug discovery and clinical development Emphasis on what results mean to the overall drug discovery process Exploration of issues in clinical trial design and conductance in each therapeutic area

This comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.

This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.

This second volume follows on from Part I by reviewing the variety of animal models of PD current available (from drosophila to rodents to non-human primate species) and their specific contributions to PD research. This is followed by comprehensive coverage of functional neuroimaging studies that explore different pathophysiological questions and evaluate treatment outcome in PD patients. Different areas of experimental therapeutics and outstanding challenges to PD treatment are presented in a concluding group of articles. Complete overview of hot topics and approaches to current PD research, from molecules, to brain circuits, to clinical and therapeutic applications Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist