Mugnier, Héloïse V.. The stabilization of chondroitinase ABC through the use of heteropolymers for the treatment of spinal cord injuries. Retrieved from https://doi.org/doi:10.7282/t3-vway-w993
DescriptionDuring the formation of a glial scar, after a spinal cord injury (SCI) is sustained, through various molecular pathways astrocytes are activated causing them to release chondroitin sulfate proteoglycans (CSPGs). This protein has inhibitory properties towards neuronal regeneration and creates a chemical barrier towards a successful healing process. The enzyme chondroitinase ABC (chABC) has shown great potential as a possible therapeutic due to its ability to degrade the glycosaminoglycan (GAG) side chains present on CSPGs neutralizing their inhibitory properties. However, at 37°C chABC is highly unstable and will lose its activity rapidly. In this project, we aim to stabilize chABC with the use of random heteropolymers designed by active machine learning models. We have explored a large chemical landscape with various monomers and degrees of polymerization (DP) to identify heteropolymers that have the ability to stabilize the enzyme. We also looked at finding a pattern in terms of monomer compositions and DPs between heteropolymers that stabilize chABC and ones that do not. Once a successful heteropolymer was identified, concentration studies, long-term studies, media assay development, and in vitro studies were completed to study these polymer-enzyme complexes (PECs).