Research Article
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Published Online: 4 July 2007

COG1410, a Novel Apolipoprotein E–Based Peptide, Improves Functional Recovery in a Murine Model of Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 24, Issue Number 7

Abstract

Traumatic brain injury (TBI) is a silent epidemic affecting approximately 1.4 million Americans annually, at an estimated annual cost of $60 billion in the United States alone. Despite an increased understanding of the pathophysiology of closed head injury, there remains no pharmacological intervention proven to improve functional outcomes in this setting. Currently, the existing standard of care for TBI consists primarily of supportive measures. Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury, where it modulates several components of the neuroinflammatory cascade associated with TBI. We have previously demonstrated that COG133, an apoE mimetic peptide, improved functional outcomes and attenuated neuronal death when administered as a single intravenous injection at 30 min post-TBI in mice. Using the principles of rational drug design, we developed a more potent analog, COG1410, which expands the therapeutic window for the treatment of TBI by a factor of four, from 30 min to 2 h. Mice that received a single intravenous injection of COG1410 at 120 min post-TBI exhibited significant improvement on a short term test of vestibulomotor function and on a long term test of spatial learning and memory. This was associated with a significant attenuation of microglial activation and neuronal death in the hippocampus, the neuroanatomical substrate for learning and memory. Rationally derived apoE mimetic peptides have been demonstrated to exert neuroprotective and anti-inflammatory effects in vitro and in clinically relevant models of brain injury. This represents a novel therapeutic strategy in the treatment of TBI.

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Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 24Issue Number 7July 2007
Pages: 1093 - 1107
PubMed: 17610350

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Published online: 4 July 2007
Published in print: July 2007

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Daniel T. Laskowitz
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina.
Suzanne E. McKenna
Cognosci, Inc., Research Triangle Park, North Carolina.
Pingping Song
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Haichen Wang
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Lori Durham
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Nolan Yeung
Cognosci, Inc., Research Triangle Park, North Carolina.
Dale Christensen
Cognosci, Inc., Research Triangle Park, North Carolina.
Michael P. Vitek
Division of Neurology, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina.
Cognosci, Inc., Research Triangle Park, North Carolina.

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