Improving And Accelerating Therapeutic Development For Nervous System Disorders

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.

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.

Despite substantial advances in developing treatments for the serious illnesses that affect people worldwide, there remains a tremendous unmet need in the treatment of complex neurologic diseases, including neuropsychiatric and neurodegenerative disorders. Chief among the challenges that have hindered the development of therapeutics for central nervous system (CNS) disorders is the bloodâ€"brain barrier (BBB). The Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine convened a workshop to explore the challenges associated with the BBB that have thus far stymied development of CNS drugs, examine new technologies that could address these challenges, and highlight potential opportunities for moving the field forward. This publication summarizes the presentations and discussions from the workshop.

Despite substantial advances in developing treatments for the serious illnesses that affect people worldwide, there remains a tremendous unmet need in the treatment of complex neurologic diseases, including neuropsychiatric and neurodegenerative disorders. Chief among the challenges that have hindered the development of therapeutics for central nervous system (CNS) disorders is the bloodâ€"brain barrier (BBB). The Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine convened a workshop to explore the challenges associated with the BBB that have thus far stymied development of CNS drugs, examine new technologies that could address these challenges, and highlight potential opportunities for moving the field forward. This publication summarizes the presentations and discussions from the workshop.

The Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders, in collaboration with the IOM Forum on Drug Discovery, Development, and Translation, convened a workshop on January 20-21, 2015, to explore policy changes that might increase private sector investment in research and development innovation that fills unmet medical needs for central nervous system (CNS) disorders. Workshop participants strategized about how to incentivize companies to fortify their CNS drug development programs, shrinking obstacles that currently deter ventures. Representatives from academia, government agencies, patient groups, and industry gathered to share information and viewpoints, and to brainstorm about budget-neutral policy changes that could help widen the pipeline toward drugs that address unmet needs for CNS disorders. This report summarizes the presentations and discussion of the workshop.

On April 23 and 24, 2019 the Forum on Neuroscience and Nervous System Disorders convened a workshop titled "Advancing Gene-Targeted Therapies for Central Nervous System Disorders" in Washington, DC. This public workshop brought together experts and key stakeholders from academia, government, industry, philanthropic foundations, and disease/patient-focused nonprofit organizations to explore approaches for advancing the development of gene-targeted therapies for central nervous system (CNS) disorders, and implications of developing these therapies. Participants explored lessons learned from both successful and unsuccessful clinical development programs; new knowledge about the genetic underpinnings of brain disorders; the current status and future potential of gene-targeted therapies for CNS disorders; challenges and potential solutions for translating preclinical findings to approved therapies; and patient and caregiver perspectives. They also discussed what will be needed to develop these therapies for common disorders such as Alzheimer's and Parkinson's disease, as well as neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism. The workshop included approaches that target both DNA and RNA, as well as gene products using viral vectors, antisense oligonucleotides, and RNA interference. This publication summarizes the presentations and discussion of the workshop.

Nervous system diseases represent a major health concern worldwide. Although important financial and professional investment, their etiology and pathophysiology still remain mostly elusive. Moreover, the clinical need of disease-modifying therapies is still unmet. In the last decades, traditional R&D has failed in identifying new effective therapies in many medical areas and drug repositioning has recently emerged as a promising alternative strategy to de novo drug discovery to improve and accelerate therapeutic development. For the first time, Drug Repositioning: Approaches and Applications for Neurotherapeutics reviews history and advances in drug repositioning, with a special focus on therapeutics for nervous system diseases. International experts from Academia, Industry and Non-profit organisations will provide different views on drug repositioning advantages, challenges and specific applications, which will be covered for nervous system diseases including Alzheimer's, Parkinson's, Huntington's diseases, Amyotrophic Lateral Sclerosis, Spinal Muscular Atrophy, ischemic stroke, and psychiatric disorders. This book provides a balanced overview and synthesis of drug repositioning concept, methods and applications for neurotherapeutics. It represents a valuable resource for students, scientists and clinicians working in academic settings, industry and government agencies within the fields of neuroscience, pharmacology, neurology, pharmaceutical sciences, drug discovery and development.

Chronic pain is one of the most prevalent, costly, and disabling health conditions in the United States. Estimates show that more than 11 percent of the American population suffer from chronic pain, yet the federal pain research investment has been minimal. In parallel with a gradual increased recognition of the problems of treating chronic pain, the opioid epidemic has emerged as a growing public health emergency. The intersection of these two crises lies in the fact that an unintended consequence of treating pain has been an increasing number of opioid prescriptions and diversion of drugs for illicit purposes. In May 2017, the National Institutes of Health (NIH), and the National Institute on Drug Abuse announced a publicâ€"private partnership to develop solutions to the opioid crisis and cut in half the time it takes to develop non-addictive analgesics. To advance the planning of NIH's anticipated publicâ€"private partnerships, the National Academies' Forum on Neuroscience and Nervous Systems Disorders hosted a public workshop that brought together a diverse group of stakeholders from academia, federal agencies, advocacy organizations and companies developing therapeutics for pain and opioid use disorders. Participants discussed potential strategies to accelerate development of non-addictive pain medications and treatments for opioid use disorders. This publication summarizes the presentations and discussions from the workshop.