scholarly journals Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

2020 ◽  
Vol 21 (23) ◽  
pp. 8896
Author(s):  
Rustem Islamov ◽  
Farid Bashirov ◽  
Filip Fadeev ◽  
Roman Shevchenko ◽  
Andrei Izmailov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Combined Treatment ◽  
Small Sample ◽  
Functional Restoration ◽  
Synaptic Proteins ◽  
Large Animal ◽  
Cord Injury ◽  
Spinal Contusion

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

scholarly journals White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury

2021 ◽  
Author(s):  
Zheng Cao ◽  
Weitao Man ◽  
Yuhui Xiong ◽  
Yi Guo ◽  
Shuhui Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Nerve Regeneration ◽  
Spinal Cord Injuries ◽  
Diffusion Tensor ◽  
Nerve Fibers ◽  
Functional Restoration ◽  
Large Animal ◽  
Cord Injury

Abstract A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact, and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.

scholarly journals Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury

2001 ◽  
Vol 533 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Leonard L. Jones ◽  
Martin Oudega ◽  
Mary Bartlett Bunge ◽  
Mark H. Tuszynski
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Neurotrophic Factors ◽  
Cord Injury

scholarly journals Planet of the AAVs: The Spinal Cord Injury Episode

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 613
Author(s):  
Katerina Stepankova ◽  
Pavla Jendelova ◽  
Lucia Machova Urdzikova
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Cell Types ◽  
Specific Cell ◽  
Adeno Associated Virus ◽  
Adequate Treatment ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Transgene Delivery

The spinal cord injury (SCI) is a medical and life-disrupting condition with devastating consequences for the physical, social, and professional welfare of patients, and there is no adequate treatment for it. At the same time, gene therapy has been studied as a promising approach for the treatment of neurological and neurodegenerative disorders by delivering remedial genes to the central nervous system (CNS), of which the spinal cord is a part. For gene therapy, multiple vectors have been introduced, including integrating lentiviral vectors and non-integrating adeno-associated virus (AAV) vectors. AAV vectors are a promising system for transgene delivery into the CNS due to their safety profile as well as long-term gene expression. Gene therapy mediated by AAV vectors shows potential for treating SCI by delivering certain genetic information to specific cell types. This review has focused on a potential treatment of SCI by gene therapy using AAV vectors.

The Hemisection Approach in Large Animal Models of Spinal Cord Injury: Overview of Methods and Applications

2018 ◽  
Vol 33 (3) ◽  
pp. 240-251
Author(s):  
S. Wilson ◽  
S. J. Nagel ◽  
L. A. Frizon ◽  
D. C. Fredericks ◽  
N. A. DeVries-Watson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Models ◽  
Large Animal ◽  
Large Animal Models ◽  
Cord Injury

scholarly journals Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury: a proof of principle study

2021 ◽  
Vol 16 (3) ◽  
pp. 550 ◽  
Author(s):  
HyunJoon Lee ◽  
RustemRobertovich Islamov ◽  
FilipOlegovich Fadeev ◽  
FaridVagizovich Bashirov ◽  
VaheArshaluysovich Markosyan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Ex Vivo ◽  
Cord Injury ◽  
Proof Of Principle

scholarly journals Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs

2020 ◽  
Vol 10 (10) ◽  
pp. 744
Author(s):  
Filip Fadeev ◽  
Anton Eremeev ◽  
Farid Bashirov ◽  
Roman Shevchenko ◽  
Andrei Izmailov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Motor Evoked Potentials ◽  
Functional Restoration ◽  
Thoracic Injury ◽  
Spinal Circuitry ◽  
Lower Amplitude ◽  
Cord Injury ◽  
Mini Pigs

This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury.

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