PRECLINICAL RESEARCH PROGRAM
As part of its preclinical research program, CNRM is in the process of refining a translational research program that will allow for successful transition of interventions from animal models to humans. The plan to achieve this involves the development of preclinical trial criteria that mirror those of human trials. They are as follows:
Preclinical Therapeutic Trials Criteria
1. Preregistration of the protocol, including primary outcome measure and sample size (e.g. Open Science Framework at https://osf.io, analogous to clinicaltrials.gov)
2. Authentication of biological reagents such as antibodies, recombinant proteins, and cell lines
5. Accounting for each animal in a CONSORT diagram
6. Time from injury to intervention realistic relative to what would be achieved in human trials (e.g. 6-8 hours for acute studies, 3-6 months after injury for late sequelae)
7. Pharmacodynamic markers of therapeutic target engagement that could be implemented in human trials (e.g. MRI, blood biomarkers, physiological tests)
8. Long-term (6-12 month) behavioral outcome measures analogous to those used in human trials
9. Safety/toxicity assessments
10. Consideration of secondary injury factors (hypoxia, hypotension, elevated ICP, other trauma)
11. Exploration of age and sex as biological variables
12. Replication within the same lab, and in an independent lab
13. Testing in a larger animal model for studies performed initially in rodents
Preclinical animal models in development
1. Mouse model of combined blast + impact + stress under development with long-term (6-12 month) behavioral assessments as primary outcomes that will measure:
Depression and anxiety-like Behavior
2. Ferret model of combined blast + impact + stress under development with long-term (6 month) behavioral assessments as primary outcomes.
Behavioral assays for social behavior, headache-related behavior, anhedonia, sleep, and activity under development.
Our focus is on efficient study design that will allow multiple therapeutic trials to be run in a staggered fashion.