COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Laskowitz, DT; McKenna, SE; Song, P; Wang, H; Durham, L; Yeung, N; Christensen, D; Vitek, MP

Published Date

  • July 2007

Published In

Volume / Issue

  • 24 / 7

Start / End Page

  • 1093 - 1107

PubMed ID

  • 17610350

Pubmed Central ID

  • 17610350

Electronic International Standard Serial Number (EISSN)

  • 1557-9042

International Standard Serial Number (ISSN)

  • 0897-7151

Digital Object Identifier (DOI)

  • 10.1089/neu.2006.0192

Language

  • eng