Chondroitinase Gene Therapy for Spinal Cord Injury
Spinal cord injury (SCI) can lead to permanent paralysis below the level of injury. Environmental factors within the injured spinal cord have been shown to strongly participate in regenerative failure. Shortly after injury, the formation of a glial-fibroblastic scar develops at the injury site. Besides isolating the injury area and stabilizing inflammation and cellular damage, the glial scar is also an important source of both the physical and molecular barriers affecting axonal regeneration. The responding reactive astrocytes are known to secrete a group of potent axonal growth-inhibitory matrix molecules known as chondroitin sulfate proteoglycans (CSPGs). The inhibitory nature of these CSPGs can be dramatically attenuated using the bacterial enzyme chondroitinase ABC. Since chondroitinase rapidly degrades, long-term studies require either (1) multiple injections of purified protein, (2) expression of the chondroitinase transgene, or (3) biodegradable scaffold to release the protein slowly. Of these options, the latter two are preferred. We have developed an easy and rapid method of analyzing the bioactivity of chondroitinase released by genetically altered cells or from a biodegradable platform.
Key wordsSpinal cord Injury Chondroitinase Glial scar Astrocyte CSPG Extracellular matrix Gene therapy
This work was funded by a grant from the National Institute of Neurological Disorders and Stroke R01 NS060784 and the Shriners Hospital for Pediatric Research grants SHC 84050 and SHC 85200 (GMS).