Excerpt

Although glutamate has a staggering array of functions, none of the top-selling CNS drugs is indicated directly for rectifying dysfunction at the glutamate synapse. Currently, three prescription drugs approved by the Food and Drug Administration (FDA)—memantine, ketamine, and D-cycloserine—have implications for diseases of glutamate or glutamate-related pathology. Many workshop participants agreed that the lack of glutamate biomarkers is the largest obstacle to increasing glutamate-specific drug development. In spite of this problem, scientific progress is close to a tipping point that will yield novel glutamate biomarkers as long as concerted efforts are undertaken by academic, government, and industry researchers, as well as by health policy makers. The stakes, in their view, are too great to disregard.

Contents

• THE NATIONAL ACADEMIES
• GLUTAMATE-RELATED BIOMARKERS IN DRUG DEVELOPMENT FOR DISORDERS OF THE NERVOUS SYSTEM PLANNING COMMITTEE
• INSTITUTE OF MEDICINE FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
• Reviewers
• 1. Introduction
  • GLUTAMATE BIOMARKERS
  • WORKSHOP GOALS
• 2. Overview of the Glutamatergic System
  • GLUTAMATE RECEPTORS
  • GLUTAMATE TRANSPORTERS
• 3. Glutamate Biomarkers
  • BIOMARKERS OF ENGAGEMENT AND EFFICACY
  • PHYSIOLOGICAL BIOMARKERS
  • COGNITIVE BIOMARKERS
  • IMAGING BIOMARKERS
• 4. Treatment Implications of Biomarkers
  • TARGET DEVELOPMENT
  • PATIENT STRATIFICATION
  • SIDE-EFFECT REDUCTION
• 5. Challenges and Opportunities
  • CHALLENGES
  • OPPORTUNITIES
  • SUMMARY
• Appendixes
  • A References
  • B Registered Attendees
  • C Agenda

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; AstraZeneca Pharmaceuticals, Inc.; CeNeRx Biopharma; the Department of Health and Human Services' National Institutes of Health (NIH, Contract No. N01-OD-4-213) through the National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Eye Institute, NIH Blueprint for Neuroscience Research, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke; Eli Lilly and Company; Foundation for the National Institutes of Health; GE Healthcare, Inc.; 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 Multiple Sclerosis Society; the National Science Foundation (Contract No. OIA-0753701); Pfizer Inc.; and the Society for Neuroscience.

Suggested citation:

IOM (Institute of Medicine). 2011. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: A Workshop Summary. Washington, DC: The National Academies Press.

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.

NOTICE: The project that is the subject of this report 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.