Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury.
Spinal cord injury (SCI) leads to robust Rho activation at the lesion site. Here, we demonstrate that BA-210, a cell-permeable fusion protein derived from C3 transferase, formulated in fibrin sealant and delivered topically onto the dura matter, diffuses into the spinal cord and inactivates Rho in a dose-dependent manner. Treatment with BA-210 in rats with thoracic spinal cord contusion increased tissue sparing around the lesion area and led to significant improvement of locomotor function. In mice, BA-210 improved functional outcome when treatment was either applied at the time of injury or delayed by 24 h. In both rats and mice, treatment with BA-210 was well tolerated. Rats gained body weight normally, and BA-210 treatment had no impact on the development of allodynia. Inactivating Rho with BA-210 holds promise for treating patients with SCI.
Lord-Fontaine
Stephanie
S
BioAxone Therapeutic Inc., Montréal, Québec, Canada.
Yang
Fan
F
Diep
Quy
Q
Dergham
Pauline
P
Munzer
Scott
S
Tremblay
Patrick
P
McKerracher
Lisa
L
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007267:Injections; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors*
D011994:Recombinant Proteins; D020741:rho GTP-Binding Proteins