Weil Institute and Michigan Medicine awarded $1.15M grant to develop preclinical model of brain injury following cardiac arrest
The team will develop and validate a large animal model of cardiac arrest with resultant severe brain injury to translate new neuroprotective therapies.
ANN ARBOR – A research team from the U-M Max Harry Weil Institute for Critical Care Research and Innovation and Michigan Medicine has received a $1.15 million, 3-year grant from the National Institute of Neurological Disorders and Stroke (NINDS) Innovation Grants to Nurture Initial Translational Efforts (IGNITE) program to develop a swine model of severe brain injury following cardiac arrest.
Currently, there are few therapies clinically proven to reduce brain injury after cardiac arrest. This is due, in large part, to the difficulty of testing new therapies for potential human use.
“Cardiac arrest large animal models that were developed to test neuroprotective therapies rely on survival and behavior assessments and are limited in their validity,” notes Dr. Cindy Hsu, Assistant Professor of Emergency Medicine and Acute Care Surgery and the Contact Principal Investigator on this IGNITE project. “Their milder brain injury, which enables the assessment of behavioral outcomes, does not accurately model the neurocognitive deficits of comatose cardiac arrest patients. Existing large animal models of cardiac arrest are also cost-prohibitive when their outcomes are measured over multiple days. This limits our ability to study a sufficient number of these animals, resulting in inadequately powered studies.”
With the support of the IGNITE grant, the research team aims to overcome these barriers by developing and validating an innovative model with more severe brain injury and whose outcomes are measured within 24 hours of cardiac arrest. Endpoints for measuring outcomes for this model will include: novel blood-based biomarkers of brain injury, early and continuous somatosensory evoked potential (brain and spinal cord responses to stimuli), and automated quantification of neurodegeneration using a novel machine learning algorithm that analyzes digital neuropathology slides of the brain.
According to Co-PI Dr. Frederick Korley, an Associate Professor of Emergency Medicine, “this model will leverage recent breakthroughs in quantifying brain injury early to develop a realistic model that is cheaper to reproduce than existing models.”
The ultimate goal of the project will be to provide future investigators with a more relevant, valid and cost-effective pipeline to test and translate their discoveries, enabling them to bring new neurotherapeutics to cardiac arrest patients who desperately need them.
The funding from NINDS is a victory not just for the research team and the future innovators and patients who could benefit from their work, but also for the Weil Institute Proposal Development Unit (PDU) and Pre-Clinical Critical Care Laboratory (PC3L) teams which had supported the project from the very beginning.
“We worked closely with the team on the original submission in 2020,” said Meagan Ramsey, PhD, manager of the PDU. “We then helped them revise the proposal based on reviewer feedback and resubmitted it in 2021.”
Weil’s PDU core has built a unique, flexible framework to help Institute members and teams collaboratively develop compelling critical care grants from the initial intake meeting to the final submission. The PD’s role in the IGNITE grant also involved analyzing the original funding opportunity to determine fit and requirements, joining meetings with the Program Officer to ensure strong alignment with NINDS priorities, participating in team meetings, and providing substantive scientific editing for all proposal files throughout the writing and revision process.
The PC3L, lead by Dr. Hakam Tiba, worked closely with Drs. Hsu and Korley to generate preliminary data that was critical to the grant. The large animal work proposed in the grant will continue to utilize the PC3L, which has developed best in class high fidelity preclinical models of critical care ranging from cardiac arrest to sepsis.
“I want to thank the Weil Institute’s PD and PC3L teams for helping to make this proposal successful,” said Dr. Hsu.
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About the Weil Institute, formerly MCIRCC
The team at the Max Harry Weil Institute for Critical Care Research and Innovation (formerly the Michigan Center for Integrative Research in Critical Care) is dedicated to pushing the leading edge of research to develop new technologies and novel therapies for the most critically ill and injured patients. Through a unique formula of innovation, integration and entrepreneurship that was first imagined by Weil, their multi-disciplinary teams of health providers, basic scientists, engineers, data scientists, commercialization coaches, donors and industry partners are taking a boundless approach to re-imagining every aspect of critical care medicine. For more information, visit weilinstitute.med.umich.edu.