Glutamate Related Biomarkers In Drug Development For Disorders Of The Nervous System

Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.

Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.

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.

This volume provides a comprehensive overview of recent advances in targeting glutamate signaling for the treatment of major psychiatric and neurological disorders. It draws on the latest findings in glutamate neurobiology and offers valuable insights into the application of translational principles in neuroscience drug discovery and development. In each chapter, glutamate as a neurotransmitter, its receptors and transporters, and their interplay with other neurotransmitters and neurotrophic factors, are discussed in the context of a specific, highly prevalent and disabling CNS disease. Most recent and detailed information is provided on Ischemic Stroke, Chronic Stress, Major Depressive Disorder, Bipolar Disorder, Autism Spectrum Disorders (ASD), Posttraumatic Stress Disorder (PTSD), Alzheimer’s Dementia, Schizophrenia, Impulsive Aggression, Substance Use Disorders (SUD), Amyotrophic Lateral Sclerosis (ALS), Chronic Pain, Multiple Sclerosis, Parkinson’s Disease, Attention Deficit Hyperactivity Disorder (ADHD), Migraine, Epilepsy and Anxiety disorders. Moreover, the book includes an extensive overview of glutamatergic treatments already available on the market, and those which are currently in pharmaceutical drug development pipelines. The primary beneficiaries will be neurology and psychiatry specialists and residents, neuroscientists, neuropharmacologists, pharmaceutical industry and clinical research organization professionals, academics, and clinicians working with psychiatric and neurological patients with comorbidities such as cardiologists, pulmonologists, and endocrinologists. This book will also appeal to psychiatry and neurology subspecialists and clinicians working in neuroscience labs seeking an easy-to-understand yet comprehensive overview of contemporary evidence-based clinical insights backed by basic science (preclinical) research evidence. Given its scope, the book is also a unique and indispensable resource for both preclinical and clinical neuroscientists, medical advisors, and clinical research specialists in the pharmaceutical industry. In addition, it will appeal to neuroscience and neuropsychopharmacology students and guide them through the complexities of glutamate involvement in the pathophysiology of the most common debilitating brain diseases with high unmet medical needs.

Toxicologists seek to better understand the myriad of mechanisms responsible for neurotoxins. Because the incidence of neurobehavioral hazards and risks of exogenous compounds (e.g., natural toxins, synthetic molecules, and therapeutic agents) remain a subject matter of interest, predictive tools have evolved, including but not limited to novel translational in vitro models, biomarkers, newer epidemiological research tools, and well-accepted best practices for diagnosing neurotoxins in clinical practice. Taken together, the foreseen need to highlight some of the more appreciated and/or emerging tactical approaches in neurotoxicology results in a "one-stop reference" book, Neurotoxins.

Advances in technology have enabled medicinal chemists to discover and formulate several highly specific, biocompatible, and non-toxic therapeutic agents for clinical applications. Nanotechnology has achieved significant progress in the last few decades and is crucial in every field of science and technology. Nanotechnology-based pharmaceuticals offer multifaceted and alternative methodologies in comparison to the limitations of many conventional clinical therapies. Expertise in designing and developing nanoformulations has helped in targeted drug delivery. Recently, the use of innovative therapeutic agents, particularly in nanomedicine, has accounted for a significant portion of the global pharmaceutical market and is predicted to continue to grow rapidly in the near future. Nanotherapeutic Strategies and New Pharmaceuticals is an accessible multi-part reference which informs the reader about several new techniques based on nanotechnology. The chapters explain relevant topics in detail. The book is designed to encourage and help undergraduate, graduate and post-graduate students in the field of nanotherapeutics, pharmaceuticals and bio-organic chemistry through the use of didactic language and simple illustrations. Part 2 of this book covers the potential of nanotherapeutics and natural therapies for treating neurological diseases, targeting ion channels, signal transduction therapy, gene therapy of single gene mutation diseases and for nanoformulations for special purposes such as wound healing and stimuli-responsive drug delivery. The book also features a chapter that summarizes the types of nanoparticles tailored for specific molecular targets that mediate different diseases. The book set serves as a textbook for students in pharmacology and medical biochemistry, as well as a quick reference for researchers on bio-organic chemistry, as well as general readers interested in nanomedicine.

Dementia, now known as major neurocognitive disorder, is not one monolithic disease. Nor is behavior disturbance driven by one particular neurocognitive dysfunction. In fact if we are able to understand it, behavior is an excellent form of nonverbal communication. There are many different causes of dementia. A major challenge with both researching and implementing interventions is viewing dementia and related behaviors as single entities. This approach leaves room for critical errors in the treatment of dementia patients, beginning with misdiagnosis. This book approaches dementia by reviewing cognitive and functional assessments to provide a more accurate diagnosis, which then allows physicians to design specific interventions that are tailored to the person and their challenges. Because person centered care is vital to quality of life and longevity to an aging patient, this understanding of individual needs is vital. Written by experts in the field, this book incorporates the latest evidence-based behavioral interventions matched to specific deficits. Behavioral management focuses not on controlling behavior, but using it to teach staff and caregivers how to interpret common actions and maximize function for people with major neurocognitive disorders. Quality of life and individualized care planning will be the theme and the book will provide practical case examples. The book begins by introducing dementia and other neurocognitive illnesses, contextualizing them both historically and contemporarily. Next, the text focuses on the comprehensive assessment of a person with neurocognitive challenges in order to identify strengths and understand what the person is trying to communicate with their behavior. This process allows individualized care planning and behavioral (non-pharmacologic) management to meet the cognitive challenges and maximize individual strengths and thereby improve outcomes, making this a cutting edge resource.