Improving the Utility and Translation of Animal Models for Nervous System Disorders

Improving the Utility and Translation of Animal Models for Nervous System Disorders PDF

Author: Institute of Medicine

Publisher: National Academies Press

Published: 2013-04-25

Total Pages: 111

ISBN-13: 0309266335

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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.

Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders

Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders PDF

Author: National Academies of Sciences, Engineering, and Medicine

Publisher: National Academies Press

Published: 2017-05-24

Total Pages: 95

ISBN-13: 0309455162

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Compared with other disease areas, central nervous system (CNS) disorders have had the highest failure rate for new compounds in advanced clinical trials. Most CNS drugs fail because of efficacy, and the core issue underlying these problems is a poor understanding of disease biology. Concern about the poor productivity in neuroscience drug development has gained intensity over the past decade, amplified by a retraction in investment from the pharmaceutical industry. This retreat by industry has been fueled by the high failure rate of compounds in advanced clinical trials for nervous system disorders. In response to the de-emphasis of CNS disorders in therapeutic development relative to other disease areas such as cancer, metabolism, and autoimmunity, the National Academies of Sciences, Engineering, and Medicine initiated a series of workshops in 2012 to address the challenges that have slowed drug development for nervous system disorders. Motivated by the notion that advances in genetics and other new technologies are beginning to bring forth new molecular targets and identify new biomarkers, the Academies hosted the third workshop in this series in September 2016. Participants discussed opportunities to accelerate early stages of drug development for nervous system disorders in the absence of animal models that reflect disease and predict efficacy. This publication summarizes the presentations and discussions from the workshop.

Central Nervous System Diseases

Central Nervous System Diseases PDF

Author: Dwaine F. Emerich

Publisher: Springer Science & Business Media

Published: 1999-11-24

Total Pages: 511

ISBN-13: 1592596916

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Prominent experimentalists critically review the animal models widely used in developing powerful new therapies for central nervous system diseases. Coverage includes novel uses of animal models of Alzheimer's, Parkinson's, and Huntington's diseases, and studies of aging. Techniques that rely heavily on behavioral analyses, as well as models developed from infusions of neurotoxins and from advances in molecular biology, are thoroughly explicated, as are models developed for more acute neurological conditions, including traumatic brain injury and stroke. Comprehensive and authoritative, Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic offers neuroscientists, pharmacologists, and interested clinicians a unique survey of the most productive animal models of the leading neurological diseases currently employed to develop today's innovative drug therapies.

Animal Models of Neurological Disorders

Animal Models of Neurological Disorders PDF

Author: Puneet Kumar Bansal

Publisher:

Published: 2017

Total Pages:

ISBN-13: 9789811059827

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This book introduces undergraduate, postgraduate and research students and scientists to animal models of neurological disorders, along with their working principle and brief procedures. Addressing all the disorders related to the central nervous system (CNS) in a single platform, on the basis of various literature surveys it describes different procedures to induce a single disease with the help of toxins/chemicals. It also includes numerous protocols for inducing single neurological diseases, thus fulfilling an urgent need for a book that makes specific procedures for neurological disorders available, so that specific disease can be induced in laboratories according to the availability of resources. Further, it acquaints readers with the pathological changes that occur in a particular neurological disorder, which reflect specific signs and symptoms of any particular disease, and examines how they affect everyday life. It is a valuable resource for researchers aiming to eradicate or improve neurological disorders by testing the benefits of different drugs.

Improving the Utility and Translation of Animal Models for Nervous System Disorders

Improving the Utility and Translation of Animal Models for Nervous System Disorders PDF

Author: Forum on Neuroscience and Nervous System Disorders

Publisher: National Academies Press

Published: 2013-04-08

Total Pages: 111

ISBN-13: 0309266343

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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.

Animal Models of Spinal Cord Repair

Animal Models of Spinal Cord Repair PDF

Author: Håkan Aldskogius

Publisher: Humana Press

Published: 2013-01-17

Total Pages: 336

ISBN-13: 9781627031981

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The development of treatment strategies that can help patients with spinal cord injury to regain lost functions and an improved quality of life is a major medical challenge, and experimental spinal cord research has to meet these challenges by resolving fundamental problems, establishing a basis for possible novel treatment strategies of spinal cord injury, and motivating their clinical translation. In Animal Models of Spinal Cord Repair, expert researchers examine a broad range of experimental models for research on spinal cord injury, how they have contributed to our current state of knowledge, and what their advantages are in the further advancement of spinal cord repair. With models from simple lamprey to non-human primates, the information presented is intended to guide the implementation of animal models for spinal cord repair as well as to raise the awareness of the relevance of experimental models which may not be in the current mainstream of this research. As a part of the Neuromethods series, this work contains the kind of detailed description and implementation advice to guarantee successful results in the laboratory. Comprehensive and cutting-edge, Animal Models of Spinal Cord Repair presents the background information and hands-on methods descriptions, as well as the basic and clinical issues, needed to stimulate and guide researchers with different backgrounds towards the development of improved strategies for functionally relevant repair of the injured human spinal cord.

Improving and Accelerating Therapeutic Development for Nervous System Disorders

Improving and Accelerating Therapeutic Development for Nervous System Disorders PDF

Author: Institute of Medicine

Publisher: National Academies Press

Published: 2014-02-06

Total Pages: 107

ISBN-13: 0309292492

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Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

Animal Experimentation: Working Towards a Paradigm Change

Animal Experimentation: Working Towards a Paradigm Change PDF

Author: Kathrin Herrmann

Publisher: BRILL

Published: 2019-04-30

Total Pages: 749

ISBN-13: 9004391193

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Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals for the sake of hoped-for benefits in humans. Despite this rationale for continued animal experimentation, shortcomings of this practice have become increasingly more apparent and well-documented. However, these limitations are not yet widely known or appreciated, and there is a danger that they may simply be ignored. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific questions, and offer a roadmap towards an animal-free world of science.

Handbook of Innovations in Central Nervous System Regenerative Medicine

Handbook of Innovations in Central Nervous System Regenerative Medicine PDF

Author: António Salgado

Publisher: Elsevier

Published: 2020-06-10

Total Pages: 712

ISBN-13: 0128180854

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Handbook of Innovations in CNS Regenerative Medicine provides a comprehensive overview of the CNS regenerative medicine field. The book describes the basic biology and anatomy of the CNS and how injury and disease affect its balance and the limitations of the present therapies used in the clinics. It also introduces recent trends in different fields of CNS regenerative medicine, including cell transplantation, bio and neuro-engineering, molecular/pharmacotherapy therapies and enabling technologies. Finally, the book presents successful cases of translation of basic research to first-in-human trials and the steps needed to follow this path. Areas such as cell transplantation approaches, bio and neuro-engineering, molecular/pharmacotherapy therapies and enabling technologies are key in regenerative medicine are covered in the book, along with regulatory and ethical issues. Describes the basic biology and anatomy of the CNS and how injury and disease affect its balance Discusses the limitations of present therapies used in the clinics Introduces the recent trends in different fields of CNS regenerative medicine, including cell transplantation, bio and neuro-engineering, molecular/pharmacotherapy therapies, and enabling technologies Presents successful cases of translation of basic research to first-in-human trials, along with the steps needed to follow this path