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.

Contents

• THE NATIONAL ACADEMIES
• PLANNING COMMITTEE ON ACCELERATING THERAPEUTIC DEVELOPMENT FOR NERVOUS SYSTEM DISORDERS TOWARD FIRST-IN-HUMAN TRIALS
• FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
• Reviewers
• 1. Introduction and Overview
  • CHALLENGES WITH THE UTILITY AND TRANSLATION OF ANIMAL MODELS
  • WORKSHOP OBJECTIVES
  • ORGANIZATION OF THE REPORT
  • TOPICS HIGHLIGHTED DURING PRESENTATIONS AND DISCUSSIONS
• 2. Drug Development Challenges
  • DRUG DISCOVERY AND DEVELOPMENT PATHWAY
  • CURRENT DRUG DEVELOPMENT CHALLENGES
  • THE REGULATORY PROCESS
• 3. Target Identification
  • STEM CELLS
  • GENETICS
  • IMAGING TECHNIQUES
• 4. Target Validation
  • EARLY VALIDATION OF TARGETS
  • A NEED FOR BETTER BIOMARKERS
  • PORTFOLIO ASSESSMENT TOOL FOR TARGET VALIDATION AND QUALIFICATION
• 5. Opportunities to Improve and Accelerate the Drug Development Pipeline
  • METHODOLOGICAL APPROACHES
  • OVERARCHING CHANGES TO THE CURRENT PIPELINE
  • INFRASTRUCTURAL OPPORTUNITIES
  • VENTURE CAPITAL PERSPECTIVE ON OPPORTUNITIES TO IMPROVE DRUG DEVELOPMENT
• 6. Perspectives on Next Steps
  • Current Therapeutic Development Practices
  • The Regulatory Pathway
  • New and Emerging Tools and Technologies
  • Opportunities in Nervous System Disorders
  • Optimizing Therapeutic Development
  • SUMMARY
• APPENDIXES
  • A References
  • B Workshop Agenda
  • C Registered Attendees

Rapporteurs: Sheena M. Posey Norris, Diana E. Pankevich, Miriam Davis, and Bruce M. Altevogt.

This project was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; CeNeRx Biopharma; the Department of Health and Human Services’ National Institutes of Health (NIH, Contract No. HHSN26300026 [Under Master Base # DHHS-10001018]) through the National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs (101-D27015); Eli Lilly and Company; Fast Forward, LLC; Foundation for the National Institutes of Health; GE Healthcare, Inc. (2580261187); GlaxoSmithKline, Inc.; Johnson & Johnson Pharmaceutical Research and Development, LLC; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; the National Science Foundation (Contract No. OIA-0753701); One Mind for Research; Pfizer Inc.; the Society for Neuroscience; and Wellcome Trust. The views presented in this publication are those of the editors and attributing authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

Suggested citation:

IOM (Institute of Medicine). 2014. Improving and accelerating therapeutic development for nervous system disorders: Workshop summary. Washington, DC: The National Academies Press.

NOTICE: The workshop that is the subject of this workshop summary was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.