title: Local inhibition of Rho signaling by cell-permeable recombinant protein BA-210 prevents secondary damage and promotes functional recovery following acute spinal cord injury.
abstract: 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.
authors.affiliation: BioAxone Therapeutic Inc., Montréal, Québec, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lord-Fontaine
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Quy
authors.initials: Q
authors.lastname: Diep
authors.forename: Pauline
authors.initials: P
authors.lastname: Dergham
authors.forename: Scott
authors.initials: S
authors.lastname: Munzer
authors.forename: Patrick
authors.initials: P
authors.lastname: Tremblay
authors.forename: Lisa
authors.initials: L
authors.lastname: McKerracher
mesh_terms: 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*
chemical_list: D011994:Recombinant Proteins; D020741:rho GTP-Binding Proteins