Improving and Accelerating Therapeutic Development for Nervous System Disorders


Book Description

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.




Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics


Book Description

Neuronal Networks in Brain Function, CNS Disorders, and Therapeutics, edited by two leaders in the field, offers a current and complete review of what we know about neural networks. How the brain accomplishes many of its more complex tasks can only be understood via study of neuronal network control and network interactions. Large networks can undergo major functional changes, resulting in substantially different brain function and affecting everything from learning to the potential for epilepsy. With chapters authored by experts in each topic, this book advances the understanding of: - How the brain carries out important tasks via networks - How these networks interact in normal brain function - Major mechanisms that control network function - The interaction of the normal networks to produce more complex behaviors - How brain disorders can result from abnormal interactions - How therapy of disorders can be advanced through this network approach This book will benefit neuroscience researchers and graduate students with an interest in networks, as well as clinicians in neuroscience, pharmacology, and psychiatry dealing with neurobiological disorders. - Utilizes perspectives and tools from various neuroscience subdisciplines (cellular, systems, physiologic), making the volume broadly relevant - Chapters explore normal network function and control mechanisms, with an eye to improving therapies for brain disorders - Reflects predominant disciplinary shift from an anatomical to a functional perspective of the brain - Edited work with chapters authored by leaders in the field around the globe – the broadest, most expert coverage available




Music, Brain, and Rehabilitation: Emerging Therapeutic Applications and Potential Neural Mechanisms


Book Description

Music is an important source of enjoyment, learning, and well-being in life as well as a rich, powerful, and versatile stimulus for the brain. With the advance of modern neuroimaging techniques during the past decades, we are now beginning to understand better what goes on in the healthy brain when we hear, play, think, and feel music and how the structure and function of the brain can change as a result of musical training and expertise. For more than a century, music has also been studied in the field of neurology where the focus has mostly been on musical deficits and symptoms caused by neurological illness (e.g., amusia, musicogenic epilepsy) or on occupational diseases of professional musicians (e.g., focal dystonia, hearing loss). Recently, however, there has been increasing interest and progress also in adopting music as a therapeutic tool in neurological rehabilitation, and many novel music-based rehabilitation methods have been developed to facilitate motor, cognitive, emotional, and social functioning of infants, children and adults suffering from a debilitating neurological illness or disorder. Traditionally, the fields of music neuroscience and music therapy have progressed rather independently, but they are now beginning to integrate and merge in clinical neurology, providing novel and important information about how music is processed in the damaged or abnormal brain, how structural and functional recovery of the brain can be enhanced by music-based rehabilitation methods, and what neural mechanisms underlie the therapeutic effects of music. Ideally, this information can be used to better understand how and why music works in rehabilitation and to develop more effective music-based applications that can be targeted and tailored towards individual rehabilitation needs. The aim of this Research Topic is to bring together research across multiple disciplines with a special focus on music, brain, and neurological rehabilitation. We encourage researchers working in the field to submit a paper presenting either original empirical research, novel theoretical or conceptual perspectives, a review, or methodological advances related to following two core topics: 1) how are musical skills and attributes (e.g., perceiving music, experiencing music emotionally, playing or singing) affected by a developmental or acquired neurological illness or disorder (for example, stroke, aphasia, brain injury, Alzheimer’s disease, Parkinson’s disease, autism, ADHD, dyslexia, focal dystonia, or tinnitus) and 2) what is the applicability, effectiveness, and mechanisms of music-based rehabilitation methods for persons with a neurological illness or disorder? Research methodology can include behavioural, physiological and/or neuroimaging techniques, and studies can be either clinical group studies or case studies (studies of healthy subjects are applicable only if their findings have clear clinical implications).




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


Book Description

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.




Translational Research in Traumatic Brain Injury


Book Description

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme




Disease Control Priorities, Third Edition (Volume 4)


Book Description

Mental, neurological, and substance use disorders are common, highly disabling, and associated with significant premature mortality. The impact of these disorders on the social and economic well-being of individuals, families, and societies is large, growing, and underestimated. Despite this burden, these disorders have been systematically neglected, particularly in low- and middle-income countries, with pitifully small contributions to scaling up cost-effective prevention and treatment strategies. Systematically compiling the substantial existing knowledge to address this inequity is the central goal of this volume. This evidence-base can help policy makers in resource-constrained settings as they prioritize programs and interventions to address these disorders.




Developing Multimodal Therapies for Brain Disorders


Book Description

Multimodal therapy approaches that combine interventions aimed at different aspects of disease are emerging as potentialâ€"and perhaps essentialâ€"ways to enhance clinical outcomes for patients with psychiatric and neurological disorders. In order to examine the general principles underlying multimodal therapies and to explore challenges, potential barriers, and opportunities for their development, the National Academies of Sciences, Engineering, and Medicine convened a workshop in June 2016. Participants explored scientific, clinical, regulatory, and reimbursement issues related to multimodal approaches and potential opportunities to enhance clinical outcomes for individuals with nervous system disorders. This publication summarizes the presentations and discussions from the workshop.




Brain Neurotrauma


Book Description

With the contribution from more than one hundred CNS neurotrauma experts, this book provides a comprehensive and up-to-date account on the latest developments in the area of neurotrauma including biomarker studies, experimental models, diagnostic methods, and neurotherapeutic intervention strategies in brain injury research. It discusses neurotrauma mechanisms, biomarker discovery, and neurocognitive and neurobehavioral deficits. Also included are medical interventions and recent neurotherapeutics used in the area of brain injury that have been translated to the area of rehabilitation research. In addition, a section is devoted to models of milder CNS injury, including sports injuries.




Precision Medicine in Stroke


Book Description

This book provides a comprehensive coverage of the state of the art in precision medicine in stroke. It starts by explaining and giving general information about precision medicine. Current applications in different strokes types (ischemic, haemorrhagic) are presented from diagnosis to treatment. In addition, ongoing research in the field (early stroke diagnosis and estimation of prognosis) is extensively discussed. The final part provides an in-depth discussion of how different interdisciplinary areas like artificial intelligence, molecular biology and genetics are contributing to this area. Precision Medicine in Stroke provides a practical approach to each chapter, reinforcing clinical applications and presenting clinical cases. This book is intended for all clinicians that interact with stroke patients (neurologists, internal medicine doctors, general practitioners, neurosurgeons), students and basic researchers.