Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury

Ephron S. Rosenzweig, Ernesto A. Salegio, Justine J. Liang, Janet L. Weber, Chase A. Weinholtz, John H. Brock, Rod Moseanko, Stephanie Hawbecker, Roger Pender, Christina L. Cruzen, Jennifer F. Iaci, Anthony O. Caggiano, Andrew R. Blight, Barbara Haenzi, J. Russell Huie, Leif A. Havton, Yvette S. Nout-Lomas, James W. Fawcett, Adam R. Ferguson, Michael S. BeattieJacqueline C. Bresnahan, Mark H. Tuszynski

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection. Four weeks after hemisection, we administered multiple intraparenchymal Chase injections below the lesion, targeting spinal cord circuits that control hand function. Hand function improved significantly in Chase-treated monkeys relative to vehicle-injected controls. Moreover, Chase significantly increased corticospinal axon growth and the number of synapses formed by corticospinal terminals in gray matter caudal to the lesion. No detrimental effects were detected. This approach appears to merit clinical translation in spinal cord injury.

Original languageEnglish
Pages (from-to)1269-1275
Number of pages7
JournalNature Neuroscience
Volume22
Issue number8
DOIs
StatePublished - 1 Aug 2019
Externally publishedYes

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