Effects of postinfarct myelin-associated glycoprotein antibody treatment on motor recovery and motor map plasticity in squirrel monkeys.
OBJECTIVE
New insights into the brain's ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage.


METHODS
Using a between-groups repeated-measures design, squirrel monkeys were randomized to 1 of 2 groups: an experimental group received intravenous GSK249320 beginning 24 hours after an ischemic infarct in motor cortex with repeated dosages given at 1-week intervals for 6 weeks and a control group received only the vehicle at matched time periods. The primary end point was a motor performance index based on a distal forelimb reach-and-retrieval task. Neurophysiological mapping techniques were used to determine changes in spared motor representations.


RESULTS
All monkeys recovered to baseline motor performance levels by postinfarct day 16. Functional recovery in the experimental group was significantly facilitated on the primary end point, albeit using slower movements. At 7 weeks post infarct, motor maps in the spared ventral premotor cortex in the experimental group decreased in area compared with the control group.


CONCLUSIONS
GSK249320, initiated 24 hours after a focal cortical ischemic infarct, facilitated functional recovery. Together with the neurophysiological data, these results suggest that GSK249320 has a substantial biological effect on spared cortical tissue. However, its mechanisms of action may be widespread and not strictly limited to peri-infarct cortex and nearby premotor areas.
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.).
Scott
S
Barbay
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.).
Erik J
EJ
Plautz
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.).
Elena
E
Zoubina
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.).
Shawn B
SB
Frost
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.).
Steven C
SC
Cramer
From the Department of Molecular and Integrative Physiology, Landon Center on Aging, University of Kansas Medical Center (S.B., E.J.P., E.Z., S.B.F., R.J.N.); and Department of Neurology and Department of Anatomy and Neurobiology, University of California, Irvine (S.C.C.). rnudo@kumc.edu.
Randolph J
RJ
Nudo
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001369:Axons / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000503:physiopathology; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology*; D009048:Motor Skills / Q000187:drug effects*; D018992:Myelin-Associated Glycoprotein / Q000037:antagonists & inhibitors*; D020127:Recovery of Function / Q000187:drug effects*; D012453:Saimiri
D061067:Antibodies, Monoclonal, Humanized; D018992:Myelin-Associated Glycoprotein; C581856:refanezumab
FAM168B protein, human; haplorhini; neuronal plasticity; neurophysiology; recovery of function; stroke