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Introduction and Overview1
Neuroinflammation is a burgeoning area of interest in academia and biopharma with a broadly acknowledged role in many central nervous system (CNS) disorders, said Rita Balice-Gordon, head of neuroscience research at Sanofi, Inc. However, she added, there is little agreement on the pathophysiological mechanisms that underlie the manifestations of neuroinflammation in the CNS compartment and how neuroinflammation operates as a driver and also as a consequence of disease in the brain. Moreover, another unclear area is how to translate increased understanding of the mechanisms that underlie neuroinflammation and its manifestations in the CNS to therapeutics. In particular, she cited the need for biomarkers that can be used as markers, not only of disease progression but of therapeutic efficacy as well, to make clinical trials and regulatory paths more straightforward.
To address these gaps in understanding mechanisms and how to translate that understanding into therapeutics, the Forum on Neuroscience and Nervous System Disorders of the National Academies of Sciences, Engineering, and Medicine convened a workshop on March 20-21, 2017, bringing together key leaders in the field from industry, academia, and governmental agencies to explore the role and mechanisms of neuroinflammation in a variety of CNS diseases. The workshop also considered strategies to advance the identification and validation of biomarkers of neuroinflammation that could accelerate development of therapies, bringing much-needed treatments to patients with disorders ranging from neuroinflammatory diseases, such as multiple sclerosis (MS), to neuropsychiatric disorders, such as depression (see Box 1-1).
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1 The planning committee’s role was limited to planning the workshop, and the Proceedings of a Workshop was prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not endorsed or verified by the National Academies of Sciences, Engineering, and Medicine, and they should not be construed as reflecting any group consensus.
WORKSHOP OBJECTIVES
This workshop was designed to identify the key questions that need to be addressed as a field to develop tractable biomarkers of neuroinflammation to assess disease progression or therapeutic efficacy, and thus to advance the development of therapeutics, said Linda Brady, director of the Division of Neuroscience and Basic Behavioral Science at the National Institute of Mental Health (NIMH). Brian Campbell, vice president of pharmacology at MindImmune Therapeutics, Inc., and George & Anne Ryan Research Professor of Neuroscience at The University of Rhode Island, gave examples of some questions. What are the unique features of neuroinflammation in acute versus chronic disease states? Are there different phenotypes that are important to measure in those conditions? What are the needs for biomarkers in acute versus chronic settings?
ORGANIZATION OF THE PROCEEDINGS
The following proceedings summarize the workshop presentations and discussions. Chapter 2 provides a summary of the myriad challenges to developing biomarkers of neuroinflammation as well as opportunities to address these challenges, as detailed in later chapters. Chapter 3 provides a primer on the mechanisms and manifestations of neuroinflammation across the acute to chronic neuroinflammation continuum. These mechanisms are further explored in Chapter 4, using as examples MS, traumatic brain injury (TBI), Huntington’s disease (HD), Alzheimer’s disease (AD), and neuropsychiatric disorders such as depression. Chapters 5 and 6 discuss neuroimaging biomarkers and fluid biomarkers of neuroinflammation, respectively. Chapter 7 offers the concluding thoughts of workshop participants on the challenges that still need to be addressed, and discusses ongoing efforts to build the collaborations to consolidate the data and expertise that will be needed to facilitate development and validation of neuroinflammatory biomarkers and to accelerate the development of new therapies.
