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Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury


The treatment of traumatic brain injury (TBI) in military populations is hindered by underreporting and underdiagnosis. Clinical symptoms and outcomes may be mitigated with an effective pre-injury prophylaxis. This study evaluates whether CN-105, a 5-amino acid apolipoprotein E (ApoE) mimetic peptide previously shown to modify the post-traumatic neuroinflammatory response, would maintain its neuroprotective effects if administered prior to closed-head injury in a clinically relevant murine model. CN-105 was synthesized by Polypeptide Inc. (San Diego, CA) and administered to C57-BL/6 mice intravenously (IV) and/or by intraperitoneal (IP) injection at various time points prior to injury while vehicle treated animals received IV and/or IP normal saline. Animals were randomized following injury and behavioral observations were conducted by investigators blinded to treatment. Vestibulomotor function was assessed using an automated Rotarod (Ugo Basile, Comerio, Italy), and hippocampal microglial activation was assessed using F4/80 immunohistochemical staining in treated and untreated mice 7 days post-TBI. Separate, in vivo assessments of the pharmacokinetics was performed in healthy CD-1. IV CN-105 administered prior to head injury improved vestibulomotor function compared to vehicle control-treated animals. CN-105 co-administered by IP and IV dosing 6 h prior to injury also improved vestibulomotor function up to 28 days following injury. Microglia counted in CN-105 treated specimens were significantly fewer (P = 0.03) than in vehicle specimens. CN-105 improves functional outcomes and reduces hippocampal microglial activation when administered prior to injury and could be adapted as a pre-injury prophylaxis for soldiers at high risk for TBI.

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Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.



Anti-access/area denial


Animal Care and Use Review Office


Analysis of variance


Apolipoprotein E


Central nervous system


Department of Defense


Low density lipoprotein receptor-related protein 1


Mean plasma residence time




Intelligence preparation of the battlefield




Phosphate buffered saline


Room temperature


Standard deviation

T 1/2 :

Terminal elimination half-life


Traumatic brain injury

T max :

Time to maximal plasma concentration


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Study drug was provided by Aegis CN, LLC. This study was supported by contract DOD CDMRP#W81XWH-16-C-0142 “Prophylactic administration of CN-105 confers neuroprotection against acute brain injury”.

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Authors and Affiliations



DVW played primary role in data analysis, writing of manuscript. HW performed animal experiments and played a role in editing. BJK played a role in data interpretation and editing. VC performed immunohistochemistry and editing of the manuscript. MM reviewed and edited the manuscript final draft. DTL played a role in experimental design, data analysis, writing and drafting.

Corresponding author

Correspondence to David Van Wyck.

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Conflict of interest

The views expressed are solely those of the authors and do not reflect the official policy or position of the US Army, US Navy, US Air Force, the Department of Defense, or the US Government. Dr. Laskowitz is an officer and has equity in Aegis CN, LLC which supplied the study drug. Dr. Wang serves as a consultant for Aegis CN, LLC. Aegis CN, LLC had no editorial control over the study design, its execution, or the writing of this manuscript. Duke University has equity and an intellectual property stake in CN-105.

Ethical approval and consent to participate

All experiments were approved by and conducted in accordance with the Duke University Institutional Animal Care and Use Committee.

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Not applicable.

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Communicated by Bill J Yates.

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Van Wyck, D., Kolls, B.J., Wang, H. et al. Prophylactic treatment with CN-105 improves functional outcomes in a murine model of closed head injury. Exp Brain Res 240, 2413–2423 (2022).

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