Forum on Neuroscience and Nervous System Disorders – författare

Autism spectrum disorders (ASD) constitute a major public health problem, affecting one in every 150 children and their families. Unfortunately, there is little understanding of the causes of ASD, and, despite their broad societal impact, many people believe that the overall research program for autism is incomplete, particularly as it relates to the role of environmental factors. The Institute of Medicine''s Forum on Neuroscience and Nervous System Disorders, in response to a request from the U.S. Secretary of Health and Human Services, hosted a workshop called "Autism and the Environment: Challenges and Opportunities for Research." The focus was on improving the understanding of the ways in which environmental factors such as chemicals, infectious agents, or physiological or psychological stress can affect the development of the brain. Autism and the Environment documents the concerted effort which brought together the key public and private stakeholders to discuss potential ways to improve the understanding of the ways that environmental factors may affect ASD. The presentations and discussions from the workshop that are described in this book identify a number of promising directions for research on the possible role of different environmental agents in the etiology of autism.

Biomarkers, or biological markers, are quantitative measurements that offer researchers and clinicians valuable insight into diagnosis, treatment and prognosis for many disorders and diseases. A major goal in neuroscience medical research is establishing biomarkers for disorders of the nervous system. Given the promising potential and necessity for neuroscience biomarkers, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders convened a public workshop and released the workshop summary entitled Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships. The workshop brought together experts from multiple areas to discuss the most promising and practical arenas in neuroscience in which biomarkers will have the greatest impact. The main objective of the workshop was to identify and discuss biomarker targets that are not currently being aggressively pursued but that could have the greatest near-term impact on the rate at which new treatments are brought forward for psychiatric and neurological disorders.

Many voluntary health organizations fund translational research. An increasing number of these organizations are looking at venture philanthropy as a critical way to advance their missions of helping patients and working to cure disease.

A wide range of participants gathered on October 3, 2008 at the Beckman Center of the National Academies of Science for a workshop titled "Venture Philanthropy Strategies Used by Patient Organizations to Support Translational Research." Participants with experience in venture philanthropy shared their experiences and lessons learned in order to improve efficiency and effectiveness in translational research.

Neuroscience has made phenomenal advances over the past 50 years and the pace of discovery continues to accelerate. On June 25, 2008, the Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders hosted more than 70 of the leading neuroscientists in the world, for a workshop titled "From Molecules to Minds: Challenges for the 21st Century." The objective of the workshop was to explore a set of common goals or "Grand Challenges" posed by participants that could inspire and rally both the scientific community and the public to consider the possibilities for neuroscience in the 21st century.

The progress of the past in combination with new tools and techniques, such as neuroimaging and molecular biology, has positioned neuroscience on the cusp of even greater transformational progress in our understanding of the brain and how its inner workings result in mental activity.

This workshop summary highlights the important issues and challenges facing the field of neuroscience as presented to those in attendance at the workshop, as well as the subsequent discussion that resulted.

As a result, three overarching Grand Challenges emerged:

Millions of people in sub-Saharan Africa suffer from mental, neurological, and substance use (MNS) disorders, and most do not have the resources to obtain treatment. The Uganda National Academy of Sciences and the Institute of Medicine hosted a workshop to discuss the state of care for MNS disorders in sub-Saharan Africa.

The Food and Drug Administration (FDA) now requires that all clinical trials for drugs that affect the central nervous system—including psychiatric drugs—are assessed for whether that drug might cause suicidal ideation or behavior. The Institute of Medicine''s (IOM) Forum on Neuroscience and Nervous System Disorders hosted a meeting on June 26, 2009, to discuss the FDA''s new policy and how to analyze best whether suicidal thoughts predict actual suicidal behavior in the near future.

Biological differences between the sexes influence not only individual health but also public health, biomedical research, and health care. The Institute of Medicine held a workshop March 8-9, 2010, to discuss sex differences and their implications for translational neuroscience research, which bridges the gap between scientific discovery and application.

Nearly 5.3 million Americans are living with Alzheimer''s disease, and 26.6 million people are affected worldwide. The Alzheimer''s Disease Neuroimaging Initiative (ADNI), a public-private partnership, provides a publicly available, international database of clinical and imaging data to foster research and collaboration on Alzheimer''s research worldwide. The Institute of Medicine held a workshop on July 12, 2010, to explore opportunities to use information from and partnerships formed because of ADNI to continue to improve the understanding and treatment of Alzheimer''s disease.

Many voluntary health organizations fund translational research. An increasing number of these organizations are looking at venture philanthropy as a critical way to advance their missions of helping patients and working to cure disease.

A wide range of participants gathered on October 3, 2008 at the Beckman Center of the National Academies of Science for a workshop titled "Venture Philanthropy Strategies Used by Patient Organizations to Support Translational Research." Participants with experience in venture philanthropy shared their experiences and lessons learned in order to improve efficiency and effectiveness in translational research.

Biomarkers, or biological markers, are quantitative measurements that offer researchers and clinicians valuable insight into diagnosis, treatment and prognosis for many disorders and diseases. A major goal in neuroscience medical research is establishing biomarkers for disorders of the nervous system. Given the promising potential and necessity for neuroscience biomarkers, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders convened a public workshop and released the workshop summary entitled Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships. The workshop brought together experts from multiple areas to discuss the most promising and practical arenas in neuroscience in which biomarkers will have the greatest impact. The main objective of the workshop was to identify and discuss biomarker targets that are not currently being aggressively pursued but that could have the greatest near-term impact on the rate at which new treatments are brought forward for psychiatric and neurological disorders.

Neuroscience has made phenomenal advances over the past 50 years and the pace of discovery continues to accelerate. On June 25, 2008, the Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders hosted more than 70 of the leading neuroscientists in the world, for a workshop titled "From Molecules to Minds: Challenges for the 21st Century." The objective of the workshop was to explore a set of common goals or "Grand Challenges" posed by participants that could inspire and rally both the scientific community and the public to consider the possibilities for neuroscience in the 21st century.

The progress of the past in combination with new tools and techniques, such as neuroimaging and molecular biology, has positioned neuroscience on the cusp of even greater transformational progress in our understanding of the brain and how its inner workings result in mental activity.

This workshop summary highlights the important issues and challenges facing the field of neuroscience as presented to those in attendance at the workshop, as well as the subsequent discussion that resulted.

As a result, three overarching Grand Challenges emerged:

Millions of people in sub-Saharan Africa suffer from mental, neurological, and substance use (MNS) disorders, and most do not have the resources to obtain treatment. The Uganda National Academy of Sciences and the Institute of Medicine hosted a workshop to discuss the state of care for MNS disorders in sub-Saharan Africa.

The Food and Drug Administration (FDA) now requires that all clinical trials for drugs that affect the central nervous system—including psychiatric drugs—are assessed for whether that drug might cause suicidal ideation or behavior. The Institute of Medicine''s (IOM) Forum on Neuroscience and Nervous System Disorders hosted a meeting on June 26, 2009, to discuss the FDA''s new policy and how to analyze best whether suicidal thoughts predict actual suicidal behavior in the near future.

Nearly 5.3 million Americans are living with Alzheimer''s disease, and 26.6 million people are affected worldwide. The Alzheimer''s Disease Neuroimaging Initiative (ADNI), a public-private partnership, provides a publicly available, international database of clinical and imaging data to foster research and collaboration on Alzheimer''s research worldwide. The Institute of Medicine held a workshop on July 12, 2010, to explore opportunities to use information from and partnerships formed because of ADNI to continue to improve the understanding and treatment of Alzheimer''s disease.

Biological differences between the sexes influence not only individual health but also public health, biomedical research, and health care. The Institute of Medicine held a workshop March 8-9, 2010, to discuss sex differences and their implications for translational neuroscience research, which bridges the gap between scientific discovery and application.

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.

Animals are widely used in neuroscience research to explore biological mechanisms of nervous system function, to identify the genetic basis of disease states, and to provide models of human disorders and diseases for the development of new treatments. To ensure the humane care and use of animals, numerous laws, policies, and regulations are in place governing the use of animals in research, and certain animal regulations have implications specific to neuroscience research.

To consider animal research regulations from a global perspective, the IOM Forum on Neuroscience and Nervous System Disorders, in collaboration with the National Research Council and the Institute for Laboratory Animal Research, held a workshop in Buckinghamshire, UK, July 26-27, 2011. The workshop brought together neuroscientists, legal scholars, administrators, and other key stakeholders to discuss current and emerging trends in animal regulations as they apply to the neurosciences. This document summarizes the workshop.

Accumulating evidence gathered over the past three decades has demonstrated a biological basis for differences between men and women with respect to clinical features and treatment responses to several neuropsychiatric, neurodevelopmental, and neurodegenerative disorders. Dramatic sex differences have also been identified in the brain transcriptomes of individuals with multiple brain disorders, including depression, posttraumatic stress disorder, and autism. The brain transcriptome includes all of the messenger RNA as well as the non-protein-coding RNA molecules expressed in brain tissue and thus represents gene activity. To explore these sex-based transcriptomic differences further, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders hosted a workshop on September 23, 2020, titled Sex Differences in Brain Disorders: Emerging Transcriptomic Evidence and Implications for Therapeutic Development. The workshop brought together a broad spectrum of stakeholders to share cutting-edge emerging evidence, discuss challenges, and identify future opportunities and potential directions. This publication summarizes the presentation and discussion of the workshop.

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.

Pharmaceutical companies, academic researchers, and government agencies such as the Food and Drug Administration and the National Institutes of Health all possess large quantities of clinical research data. If these data were shared more widely within and across sectors, the resulting research advances derived from data pooling and analysis could improve public health, enhance patient safety, and spur drug development. Data sharing can also increase public trust in clinical trials and conclusions derived from them by lending transparency to the clinical research process. Much of this information, however, is never shared. Retention of clinical research data by investigators and within organizations may represent lost opportunities in biomedical research. Despite the potential benefits that could be accrued from pooling and analysis of shared data, barriers to data sharing faced by researchers in industry include concerns about data mining, erroneous secondary analyses of data, and unwarranted litigation, as well as a desire to protect confidential commercial information. Academic partners face significant cultural barriers to sharing data and participating in longer term collaborative efforts that stem from a desire to protect intellectual autonomy and a career advancement system built on priority of publication and citation requirements. Some barriers, like the need to protect patient privacy, pre- sent challenges for both sectors. Looking ahead, there are also a number of technical challenges to be faced in analyzing potentially large and heterogeneous datasets.

This public workshop focused on strategies to facilitate sharing of clinical research data in order to advance scientific knowledge and public health. While the workshop focused on sharing of data from preplanned interventional studies of human subjects, models and projects involving sharing of other clinical data types were considered to the extent that they provided lessons learned and best practices. The workshop objectives were to examine the benefits of sharing of clinical research data from all sectors and among these sectors, including, for example: benefits to the research and development enterprise and benefits to the analysis of safety and efficacy. Sharing Clinical Research Data: Workshop Summary identifies barriers and challenges to sharing clinical research data, explores strategies to address these barriers and challenges, including identifying priority actions and "low-hanging fruit" opportunities, and discusses strategies for using these potentially large datasets to facilitate scientific and public health advances.

While significant progress has been seen in fields such as cardiovascular medicine and cancer in improving patient stratification and developing targeted drugs based on genetic findings, progress continues to lag for neuropsychiatric disorders. To address this issue, the National Academies of Sciences, Engineering, and Medicine''s Forum on Neuroscience and Nervous System Disorders convened a workshop in October 2021.

The workshop brought together government, philanthropic foundations, and disease-focused non--profit organizations to discuss new genetic and neuroscience technologies and explore how they can be used to elucidate disease mechanisms and to advance the development of biomarkers and targeted therapies for people with neurological and psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop.