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. Beattie; Jacqueline C. Bresnahan; Mark H. Tuszynski

doi:10.1038/s41593-019-0424-1

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

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103 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 language	English
Pages (from-to)	1269-1275
Number of pages	7
Journal	Nature Neuroscience
Volume	22
Issue number	8
DOIs	https://doi.org/10.1038/s41593-019-0424-1
State	Published - 1 Aug 2019
Externally published	Yes

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Rosenzweig, E. S., Salegio, E. A., Liang, J. J., Weber, J. L., Weinholtz, C. A., Brock, J. H., Moseanko, R., Hawbecker, S., Pender, R., Cruzen, C. L., Iaci, J. F., Caggiano, A. O., Blight, A. R., Haenzi, B., Huie, J. R., Havton, L. A., Nout-Lomas, Y. S., Fawcett, J. W., Ferguson, A. R., ... Tuszynski, M. H. (2019). Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury. Nature Neuroscience, 22(8), 1269-1275. https://doi.org/10.1038/s41593-019-0424-1

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title = "Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = aug,

day = "1",

doi = "10.1038/s41593-019-0424-1",

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Rosenzweig, ES, Salegio, EA, Liang, JJ, Weber, JL, Weinholtz, CA, Brock, JH, Moseanko, R, Hawbecker, S, Pender, R, Cruzen, CL, Iaci, JF, Caggiano, AO, Blight, AR, Haenzi, B, Huie, JR, Havton, LA, Nout-Lomas, YS, Fawcett, JW, Ferguson, AR, Beattie, MS, Bresnahan, JC & Tuszynski, MH 2019, 'Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury', Nature Neuroscience, vol. 22, no. 8, pp. 1269-1275. https://doi.org/10.1038/s41593-019-0424-1

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AU - Rosenzweig, Ephron S.

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AU - Cruzen, Christina L.

AU - Iaci, Jennifer F.

AU - Caggiano, Anthony O.

AU - Blight, Andrew R.

AU - Haenzi, Barbara

AU - Huie, J. Russell

AU - Havton, Leif A.

AU - Nout-Lomas, Yvette S.

AU - Fawcett, James W.

AU - Ferguson, Adam R.

AU - Beattie, Michael S.

AU - Bresnahan, Jacqueline C.

AU - Tuszynski, Mark H.

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N2 - 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.

AB - 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.

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Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury

Abstract

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