Local and Sustained Release of ChondroitinaseABC-37 to the Chronically-Injured Spinal Cord
Spinal Research
University of Toronto
Chondroitinase ABC (ChASE) is a potent enzyme that has repeatedly shown great promise in spinal cord injury; yet, its inherent instability and the few choices for sustained delivery have limited clinical translation.  We invented a more stable and active form of ChASE, ChASE37, and a strategy for sustained local delivery based on affinity release (AR). We propose to take advantage of these inventions and test ChASE37-AR first in rats and then in dogs.  Four weeks after a moderate spinal cord contusion model in the rat, we will test intraparenchymal vs. subarachnoid delivery of ChASE37-AR, using ultrasound to guide the injection. We will examine functional recovery prior to and post-treatment using an array of motor (Digigait, ladder walk, BBB) and sensory (pain) assays. Using chronic spinal cord injured rats, we will also compare our previously-designed methylcellulose-based delivery vehicle with a newly designed dextrin-based vehicle for biocompatibility, to ensure that we use the optimal vehicle and delivery strategy.  We will be in a strong position to advance toward the clinic with continued guidance and engagement from our clinical co-PI, 2 patents on ChASE37 and the affinity release strategy, and behavioural improvements in rats.
5.1 Pharmaceuticals