Identification of neuroprotective properties of anti-MAG antibody: a novel approach for the treatment of stroke?
The inhibitory activity of myelin-associated glycoprotein (MAG) on neurons is thought to contribute to the lack of regenerative capacity of the CNS after injury. The interaction of MAG and its neuronal receptors mediates bidirectional signaling between neurons and oligodendrocytes. The novel finding that an anti-MAG monoclonal antibody not only possesses the ability to neutralise the inhibitory effect of MAG on neurons but also directly protects oligodendrocytes from glutamate-mediated oxidative stress-induced cell death is reported here. Furthermore, administration of anti-MAG antibody (centrally and systemically) starting 1 hour after middle cerebral artery occlusion in the rat significantly reduced lesion volume at 7 days. This neuroprotection was associated with a robust improvement in motor function compared with animals receiving control IgG1. Together, these data highlight the potential for the use of anti-MAG antibodies as therapeutic agents for the treatment of stroke.
Irving
Elaine A
EA
Neurology & GI CEDD, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Harlow, Essex, UK. Elaine_A_Irving@gsk.com
Vinson
Mary
M
Rosin
Claudia
C
Roberts
Jenny C
JC
Chapman
Debra M
DM
Facci
Laura
L
Virley
David J
DJ
Skaper
Stephen D
SD
Burbidge
Stephen A
SA
Walsh
Frank S
FS
Hunter
A Jacqueline
AJ
Parsons
Andrew A
AA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001921:Brain / Q000473:pathology / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018992:Myelin-Associated Glycoprotein; D018696:Neuroprotective Agents; D018698:Glutamic Acid