ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Combining Constitutively Active Rheb Expression and Chondroitinase Promotes Functional Axonal Regeneration after Cervical Spinal Cord Injury.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Biological engineering approaches for modulating the pathological microenvironment and promoting axonal regeneration after spinal cord injury.Frontiers in neuroscience · 2025Review
- Axonal growth inhibitors and their receptors in spinal cord injury: from biology to clinical translation.Neural regeneration research · 2023Review
- Progression in translational research on spinal cord injury based on microenvironment imbalance.Bone research · 2022Review
- Article
- Bridging the gap of axonal regeneration in the central nervous system: A state of the art review on central axonal regeneration.Frontiers in neuroscience · 2022Review
- Article
- Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury.Nature communications · 2020Article
- Grafting Embryonic Raphe Neurons Reestablishes Serotonergic Regulation of Sympathetic Activity to Improve Cardiovascular Function after Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- AKT3 Gene Transfer Promotes Anabolic Reprogramming and Photoreceptor Neuroprotection in a Pre-clinical Model of Retinitis Pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Knockdown of Fidgetin Improves Regeneration of Injured Axons by a Microtubule-Based Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- GSK3-CRMP2 signaling mediates axonal regeneration induced byCommunications biology · 2019Article
- Stem Cells from Human Exfoliated Deciduous Teeth Modulate Early Astrocyte Response after Spinal Cord Contusion.Molecular neurobiology · 2019Article
- Perspectives of RAS and RHEB GTPase Signaling Pathways in Regenerating Brain Neurons.International journal of molecular sciences · 2018Review
- Global Connectivity and Function of Descending Spinal Input Revealed by 3D Microscopy and Retrograde Transduction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Cell-type specific expression of constitutively-active Rheb promotes regeneration of bulbospinal respiratory axons following cervical SCI.Experimental neurology · 2018Article
- The transplantation of human urine stem cells combined with chondroitinase ABC promotes brain-derived neurotrophic factor and nerve growth factor following spinal cord injury in rats.International journal of clinical and experimental pathology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
After spinal cord injury (SCI), severed axons in the adult mammalian CNS are unable to mount a robust regenerative response. In addition, the glial scar at the lesion site further restricts the regenerative potential of axons. We hypothesized that a combinatorial approach coincidentally targeting these obstacles would promote axonal regeneration. We combined (1) transplantation of a growth-permissive peripheral nerve graft (PNG) into an incomplete, cervical lesion cavity; (2) transduction of neurons rostral to the SCI site to express constitutively active Rheb (caRheb; a Ras homolog enriched in brain), a GTPase that directly activates the growth-promoting pathway mammalian target of rapamycin (mTOR) via AAV-caRheb injection; and (3) digestion of growth-inhibitory chondroitin sulfate proteoglycans within the glial scar at the distal PNG interface using the bacterial enzyme chondroitinase ABC (ChABC). We found that expressing caRheb in neurons post-SCI results in modestly yet significantly more axons regenerating across a ChABC-treated distal graft interface into caudal spinal cord than either treatment alone. Excitingly, we found that caRheb+ChABC treatment significantly potentiates the formation of synapses in the host spinal cord and improves the animals' ability to use the affected forelimb. Thus, this combination strategy enhances functional axonal regeneration following a cervical SCI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.