Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Jordan W Squair^#^{1

2

3}, Marco Milano^#^{1

3}, Alexandra de Coucy^{1

3}, Matthieu Gautier^{1

3}, Michael A Skinnider^{1

3}, Nicholas D James^{1

3}, Newton Cho^{1

3}, Anna Lasne^{1

3}, Claudia Kathe^{1

3}, Thomas H Hutson^{1

3

4}, Steven Ceto^{1

3}, Laetitia Baud^{1

3}, Katia Galan^{1

3}, Viviana Aureli^{1

2

3

5}, Achilleas Laskaratos^{3

5}, Quentin Barraud^{1

3}, Timothy J Deming⁶, Richie E Kohman⁴, Bernard L Schneider^{1

7

8}, Zhigang He⁹, Jocelyne Bloch^{1

2

3

5}, Michael V Sofroniew^#¹⁰, Gregoire Courtine^#^{1

2

3

5}, Mark A Anderson^#^{1

3

4

5}

Affiliations

¹ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
² Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
³ Defitech Center for Interventional Neurotherapies (NeuroRestore), CHUV/UNIL/EPFL, 1005 Lausanne, Switzerland.
⁴ Wyss Center for Bio and Neuroengineering, 1202 Geneva, Switzerland.
⁵ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
⁶ Departments of Bioengineering, Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Bertarelli Platform for Gene Therapy, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
⁸ Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
⁹ F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

^# Contributed equally.

PMID: 37733871
DOI: 10.1126/science.adi6412

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Jordan W Squair et al. Science. 2023.

. 2023 Sep 22;381(6664):1338-1345.

doi: 10.1126/science.adi6412. Epub 2023 Sep 21.

Authors

Affiliations

¹ NeuroX Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
² Department of Neurosurgery, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
³ Defitech Center for Interventional Neurotherapies (NeuroRestore), CHUV/UNIL/EPFL, 1005 Lausanne, Switzerland.
⁴ Wyss Center for Bio and Neuroengineering, 1202 Geneva, Switzerland.
⁵ Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), 1005 Lausanne, Switzerland.
⁶ Departments of Bioengineering, Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Bertarelli Platform for Gene Therapy, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
⁸ Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
⁹ F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

^# Contributed equally.

PMID: 37733871
DOI: 10.1126/science.adi6412

Abstract

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.

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Comment in

Regrowth and recovery in mice with spinal cord injury.
Fyfe I. Fyfe I. Nat Rev Neurol. 2023 Nov;19(11):637. doi: 10.1038/s41582-023-00890-3. Nat Rev Neurol. 2023. PMID: 37813952 No abstract available.

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Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Affiliations

Recovery of walking after paralysis by regenerating characterized neurons to their natural target region

Authors

Affiliations

Abstract

Comment in

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases