GSK249320, A Monoclonal Antibody Against the Axon Outgrowth Inhibition Molecule Myelin-Associated Glycoprotein, Improves Outcome of Rodents with Experimental Stroke
Journal Title: Journal of Neurology and Experimental Neuroscience - Year 2016, Vol 2, Issue 2
Abstract
Myelin-associated glycoprotein (MAG) is an inhibitor of axon growth. MAG levels increase after stroke. GSK249320 is a monoclonal antibody that neutralizes MAG-mediated inhibition and so may promote axon outgrowth and improve post-stroke outcomes. The current study tested the hypothesis that GSK249320 initiated 24 hours or 7 days after experimental stroke improves behavioural outcomes. Rats with right middle cerebral artery occlusion for 90 minutes were randomized to receive 6 weeks of intravenous (a) GSK249320 starting 24 hours post-stroke, (b) GSK249320 starting 7 days post-stroke, or (c) vehicle. Behavioral testing was performed over 7 weeks. Serial MRI demonstrated no differences in infarct volume across groups. Animals treated with GSK249320 24 hours post-stroke showed larger increases in Neuroscore (time X group, p = 0.0008) and staircase test (main effect of group, p = 0.0214) as compared to controls, but animals treated 7 days post-stroke showed no significant behavioral benefit. No significant results were found for the sticky tape or cylinder tests. A separate set of animals with experimental stroke received a single intravenous dose of GSK249320 or vehicle at 1 hour, 24 hours, 48 hours or 1 week poststroke, and immunohistochemistry methods were used to measure GSK249320 distribution; GSK249320 was found in the ipsilesional hemisphere only, the extent of which increased with later times of injection. These data suggest that intravenous GSK249320 penetrates the lesion site and is associated with a small effect on functional outcomes when initiated 24 hours post-stroke and so support the translational potential of this monoclonal antibody as a restorative therapy for patients with stroke.
Authors and Affiliations
Diana Cash, Alanna C. Easton, Michel Mesquita, John Beech, Steve Williams, Andrew Lloyd, Elaine Irving, Steven C. Cramer
Keywords
Related Articles
- EP ID EP223845
- DOI 10.17756/jnen.2016-014
- Views 124
- Downloads 0
Stroke Survivors: Needs, Wellness and Warning Signs in a Stroke Support Group Population
Aim: This study was designed to investigate needs of stroke survivors in stroke support groups, including their knowledge of warning signs, and the effectiveness of their care provider in acquiring rehabilitation service...
Cerebral Venous and Dural Sinus Thrombosis as a Rare Cause of Subarachnoid Haemorrhage in a Patient with Stable Crohn’s Disease - A Case Report
Subarachnoid haemorrhage is a known but rare manifestation of cerebral venous and dural sinus thrombosis. We present a case of a 62-year-old female with stable Crohn’s disease, who developed thunderclap headache with nau...
Sampling an Intrinsic Foot Muscle Improves Electrodiagnostic Sensitivity for Peripheral Neuropathy
Routinely performed electrodiagnostic study may be normal in some subjects with mild peripheral neuropathy such as acral dysesthesia and/or weakness and, therefore, fails to confirm the diagnosis at the early stage. Aimi...
Cane Use in Patients with Parkinson’s Disease
Introduction: Previous studies have primarily focused on whether there were any differences between walking with and without a cane. A small amount of studies examined properties of the canes used for patients with Parki...
Acknowledgement of Manuscript Reviewers JNEN Volume-4 (2018)
The Editors of Journal of Neurology and Experimental Neuroscience (JNEN) would like to express their tremendous gratitude to all those individuals who participated in the peer review process during the preparation of thi...