scholarly journals Pharmacological, Cell, and Gene Therapy Strategies to Promote Spinal Cord Regeneration

2002 ◽  
Vol 11 (6) ◽  
pp. 593-613 ◽  
Author(s):  
Bas Blits ◽  
Gerard J. Boer ◽  
Joost Verhaagen

In this review, recent studies using pharmacological treatment, cell transplantation, and gene therapy to promote regeneration of the injured spinal cord in animal models will be summarized. Pharmacological and cell transplantation treatments generally revealed some degree of effect on the regeneration of the injured ascending and descending tracts, but further improvements to achieve a more significant functional recovery are necessary. The use of gene therapy to promote repair of the injured nervous system is a relatively new concept. It is based on the development of methods for delivering therapeutic genes to neurons, glia cells, or nonneural cells. Direct in vivo gene transfer or gene transfer in combination with (neuro)transplantation (ex vivo gene transfer) appeared powerful strategies to promote neuronal survival and axonal regrowth following traumatic injury to the central nervous system. Recent advances in understanding the cellular and molecular mechanisms that govern neuronal survival and neurite outgrowth have enabled the design of experiments aimed at viral vector-mediated transfer of genes encoding neurotrophic factors, growth-associated proteins, cell adhesion molecules, and antiapoptotic genes. Central to the success of these approaches was the development of efficient, nontoxic vectors for gene delivery and the acquirement of the appropriate (genetically modified) cells for neurotransplantation. Direct gene transfer in the nervous system was first achieved with herpes viral and E1-deleted adenoviral vectors. Both vector systems are problematic in that these vectors elicit immunogenic and cytotoxic responses. Adeno-associated viral vectors and lentiviral vectors constitute improved gene delivery systems and are beginning to be applied in neuroregeneration research of the spinal cord. Ex vivo approaches were initially based on the implantation of genetically modified fibroblasts. More recently, transduced Schwann cells, genetically modified pieces of peripheral nerve, and olfactory ensheathing glia have been used as implants into the injured spinal cord.

1997 ◽  
Vol 3 (3) ◽  
pp. E4 ◽  
Author(s):  
Gordon Tang ◽  
E. Antonio Chiocca

Gene transfer offers the potential to explore basic physiological processes and to intervene in human disease. The central nervous system (CNS) presents a fertile field in which to develop novel therapeutic modalities to treat intractable and pervasive malignant tumors and neurodegenerative disease. The extension of gene therapy to the CNS, however, faces the delivery obstacles of a target population that is postmitotic and isolated behind a blood-brain barrier (BBB). Approaches to this problem have included grafting of genetically modified cells to deliver novel proteins or introducing genes by viral or synthetic vectors geared toward the CNS cell population. Direct inoculation and bulk flow, as well as osmotic and pharmacological disruption, have been used to circumvent the BBB's exclusionary role. Once the gene is delivered, myriad strategies have been used to affect a therapeutic result. Genes activating prodrugs are the most common antitumor approach. Other approaches focus on activating immune responses, targeting angiogenesis, and influencing apoptosis and tumor suppression. At this time, therapy directed at neurodegenerative diseases has centered on ex vivo gene therapy for supply of trophic factors to promote neuronal survival, axonal outgrowth, and target tissue function. Despite early promise, gene therapy for CNS disorders will require advancements in methods for delivery and long-term expression before becoming feasible for human disease.


2006 ◽  
Vol 198 (1) ◽  
pp. 88-100 ◽  
Author(s):  
Alpa A. Trivedi ◽  
Takuji Igarashi ◽  
Nathalie Compagnone ◽  
Xiaoqing Fan ◽  
Jung-Yu C. Hsu ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Anastasiia O. Sosnovtseva ◽  
Olga V. Stepanova ◽  
Aleksei A. Stepanenko ◽  
Anastasia D. Voronova ◽  
Andrey V. Chadin ◽  
...  

The regeneration of nerve tissue after spinal cord injury is a complex and poorly understood process. Medication and surgery are not very effective treatments for patients with spinal cord injuries. Gene therapy is a popular approach for the treatment of such patients. The delivery of therapeutic genes is carried out in a variety of ways, such as direct injection of therapeutic vectors at the site of injury, retrograde delivery of vectors, and ex vivo therapy using various cells. Recombinant adenoviruses are often used as vectors for gene transfer. This review discusses the advantages, limitations and prospects of adenovectors in spinal cord injury therapy.


2002 ◽  
Vol 9 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Anders Høgset ◽  
Birgit Øvstebø Engesæter ◽  
Lina Prasmickaite ◽  
Kristian Berg ◽  
Øystein Fodstad ◽  
...  

2021 ◽  
Vol 18 ◽  
pp. 347-354
Author(s):  
Masashi Noda ◽  
Kohei Tatsumi ◽  
Hideto Matsui ◽  
Yasunori Matsunari ◽  
Takeshi Sato ◽  
...  

2021 ◽  
Vol 16 (3) ◽  
pp. 550 ◽  
Author(s):  
HyunJoon Lee ◽  
RustemRobertovich Islamov ◽  
FilipOlegovich Fadeev ◽  
FaridVagizovich Bashirov ◽  
VaheArshaluysovich Markosyan ◽  
...  

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