Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions
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Published:2021-07
Issue:S1
Volume:35
Page:68-85
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ISSN:1541-6933
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Container-title:Neurocritical Care
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language:en
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Short-container-title:Neurocrit Care
Author:
Edlow Brian L.ORCID, Sanz Leandro R. D., Polizzotto Len, Pouratian Nader, Rolston John D., Snider Samuel B., Thibaut Aurore, Stevens Robert D., Gosseries Olivia, Akbari Yama, Bleck Thomas P., Diringer Michael N., Foreman Brandon, Hartings Jed A., Helbok Raimund, Hemphill J. Claude, Ling Geoffrey S. F., Mayer Stephan A., McNett Molly, Monti Martin M., Olson DaiWai M., Owen Adrian M., Park Soojin, Provencio J. Javier, Puybasset Louis, Vespa Paul, Wagner Amy, Whyte John, Ziai Wendy,
Abstract
Abstract
Background/Objective
For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis.
Methods
We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development.
Results
Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints.
Conclusions
This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC.
Funder
Neurocritical Care Society National Institute of Neurological Disorders and Stroke NIH Office of the Director Belgian National Fund for Scientific Research King Baudouin Foundation United States H2020 Marie Skłodowska-Curie Actions James S. McDonnell Foundation Tiny Blue Dot Foundation Mind Science Foundation BIAL Foundation AstraZeneca Foundation
Publisher
Springer Science and Business Media LLC
Subject
Critical Care and Intensive Care Medicine,Neurology (clinical)
Reference240 articles.
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