The Novel Apolipoprotein E–Based Peptide COG1410 Improves Sensorimotor Performance and Reduces Injury Magnitude following Cortical Contusion Injury

Abstract

It has previously been shown that small peptide molecules derived from the apolipoprotein E (ApoE) receptor binding region are anti-inflammatory in nature and can improve outcome following head injury. The present study evaluated the preclinical efficacy of COG1410, a small molecule ApoE-mimetic peptide (1410 daltons), following cortical contusion injury (CCI). Animals were prepared with a unilateral CCI of the sensorimotor cortex (SMC) or sham procedure. Thirty mins post-CCI the animals received i.v. infusions of 0.8 mg/kg COG1410, 0.4 mg/kg COG1410, or vehicle. Starting on day 2, the animals were tested on a battery of behavioral measures to assess sensorimotor (vibrissae-forelimb placing and forelimb use-asymmetry), and motor (tapered balance beam) performance. Administration of the 0.8 mg/kg dose of COG1410 significantly improved recovery on the vibrissae-forelimb and limb asymmetry tests. However, no facilitation was observed on the tapered beam. The low dose (0.4 mg/kg) of COG1410 did not show any significant differences compared to vehicle. Lesion analysis revealed that the 0.8 mg/kg dose of COG1410 significantly reduced the size of the injury cavity compared to the 0.4 mg/kg dose and vehicle. The 0.8 mg/kg dose also reduced the number of glial fibrillary acid protein (GFAP+) reactive cells in the injured cortex. These results suggest that a single dose of COG1410 facilitates behavioral recovery and provides neuroprotection in a dose and task-dependent manner. Thus, the continued clinical development of ApoE based therapeutics is warranted and could represent a novel strategy for the treatment of traumatic brain injuries.

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat

“…This test has been previously shown to be a sensitive assessment of somatosensory and attentional deficits following injury to the frontal lobes and has been described in detail (Schallert et al, 2000, Hoane et al, 2003, Schallert and Woodlee, 2005, Hoane et al, 2006c, Hoane et al, 2007. A slightly modified version of this task was used in this experiment.…”

“…Sensorimotor function was evaluated by scoring the forelimb placing reaction (Schallert et al, 2000, Schallert and Woodlee, 2005, Hoane et al, 2006c, Hoane et al, 2007. Each rat was held by the trunk ensuring the forelimbs were free to move.…”

Apolipoprotein E mimetic peptide, CN‐105, improves outcomes in ischemic stroke

“…To overcome this limitation, smaller apoE‐mimetic peptides, derived from the helical receptor binding region of apoE, have been developed that retain the functional effects of the holoprotein on receptor binding29 in reducing inflammation17 and neuronal excitotoxicity 30. Moreover, these apoE‐mimetic compounds have demonstrated long‐term functional and histological improvements in preclinical models of ischemic stroke31, 32 and numerous other acute CNS injuries33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 (Table 1). …”

SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma: a predictor of aggressive disease and a new treatment target

“…The membrane was incubated overnight at 4°C in the primary antibody of one species and a loading control (usually GAPDH) antibody of a second species diluted in SuperBlock. 18 We washed membranes with TBST for 1 hour and incubated with the appropriate IRDye 680 or IRDye 800 secondary antibodies to detect the primary and loading control antibodies. The membranes were washed thoroughly, and protein bands were visualized and quantitated (Odyssey Infrared scanner, LI-COR).…”