Controlled release of chondroitinase ABC from fibrin gel reduces the level of inhibitory glycosaminoglycan chains in lesioned spinal cord.
Chondroitinase ABC (ChABC) is a bacterial enzyme that can enhance plasticity following injury to the central nervous system (CNS) by degrading the glycosaminoglycan (GAG) side chains of proteoglycans. CNS lesions treated with ChABC often show enhanced axonal sprouting and improved functional recovery and there is therefore much interest in the potential use of ChABC as a clinical treatment in humans. When highly concentrated fibrin gel containing ChABC was implanted adjacent to a spinal cord lesion, bioactive ChABC was detectable in the spinal cord for at least three weeks. Nearly six times more bioactive ChABC was detected in the spinal cord 3 weeks after injury when the fibrin delivery system was used vs. an intraspinal injection of ChABC (61+/-30 mU vs. 11+/-4 mU). Furthermore, 3 weeks after injury the level of inhibitory GAG found in injured spinal cord treated with the delivery system was 37% lower than the level of GAG in spinal cord treated with an injection of ChABC. When using the delivery system, 24.4% of the initial ChABC dose could still be detected in the lesion after 3 weeks, compared to just 4.4% when using an intraspinal injection of ChABC.
Hyatt
Alex J T
AJ
Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 0PY, United Kingdom.
Wang
Difei
D
Kwok
Jessica C
JC
Fawcett
James W
JW
Martin
Keith R
KR
D000180:Acrylic Resins; D000818:Animals; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D005782:Gels; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors*; D015552:Injections, Intralesional; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D006025:Glycosaminoglycans; C016680:polyacrylamide gels; D005337:Fibrin; D019765:Chondroitin ABC Lyase