Advances in chondroitinase delivery for spinal cord repair

Abstract

Chondroitin sulfate proteoglycans (CSPGs) present a formidable barrier to regrowing axons following spinal cord injury. CSPGs are secreted in response to injury and their glycosaminoglycan (GAG) side chains present steric hindrance preventing the growth of axons through the lesion site. The enzyme chondroitinase has been proven effective at reducing the CSPG GAG chains, however, there are issues with direct administration of the enzyme specifically due to its limited timeframe of activity. In this perspective article, we discuss the evolution of chondroitinase-based therapy in spinal cord injury as well as up-to-date advances on this critical therapeutic. We describe the success and the limitations around use of the bacterial enzyme namely issues around thermostability. We then discuss current efforts to improve delivery of chondroitinase with a push towards gene therapy, namely through the use of lentiviral and adeno-associated viral vectors, including the temporal modulation of its expression and activity. As a chondroitinase therapy for spinal cord injury inches nearer to the clinic, the drive towards an optimised delivery platform is currently underway.

Keywords

• chondroitinase
• cspgs
• gene therapy
• spinal cord injury
• viral vectors