Laboratory of Developmental Neurobiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States; Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
Caitlin P Mencio
Laboratory of Developmental Neurobiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States
Amanda C Barber
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
Keith R Martin
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
The failure of mammalian CNS neurons to regenerate their axons derives from a combination of intrinsic deficits and extrinsic factors. Following injury, chondroitin sulfate proteoglycans (CSPGs) within the glial scar inhibit axonal regeneration, an action mediated by the sulfated glycosaminoglycan (GAG) chains of CSPGs, especially those with 4-sulfated (4S) sugars. Arylsulfatase B (ARSB) selectively cleaves 4S groups from the non-reducing ends of GAG chains without disrupting other, growth-permissive motifs. We demonstrate that ARSB is effective in reducing the inhibitory actions of CSPGs both in in vitro models of the glial scar and after optic nerve crush (ONC) in adult mice. ARSB is clinically approved for replacement therapy in patients with mucopolysaccharidosis VI and therefore represents an attractive candidate for translation to the human CNS.
