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Compositions and methods for treatment of spinal cord injury

A technique for spinal cord injury, composition, applied in the field of compositions and methods for treating spinal cord injury, capable of addressing lack of success, no recovery of neurological function, no evidence of growth/extension of neurons and/or axons across the injury site, etc. question

Pending Publication Date: 2020-11-03
ANGIOCRINE BIOSCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although some sprouting of neurofilament-positive cells was observed, no evidence of neuronal and / or axonal growth / extension across the injury site was reported, nor was neurological recovery reported (Rauch et al., 2009)
Given the lack of success of current cell therapy attempts, there remains a need in the art for robust and effective cell therapies that can achieve functional spinal cord repair

Method used

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  • Compositions and methods for treatment of spinal cord injury
  • Compositions and methods for treatment of spinal cord injury
  • Compositions and methods for treatment of spinal cord injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] Materials and methods

[0092] Overview of Materials and Methods

[0093] Animal model: adult female Sprague-Dawley rats. Injury Model: Mid neck (C3-4) unilateral contusion. Treatment: Injection of EC alone, or in combination with NPC. Duration of treatment: Single delivery 1 week after injury. Therapeutic dose: 10 microliters containing 100,000 cells / ul culture medium (HBSS). Administration route: Inject directly into the affected area. Delivery method: Injection via a surgical syringe (Hamilton) with a 30 gauge steel needle. Experimental time: 7 weeks after injury. Anatomical Outcome Determination: Neuroanatomical Tracing and Immunohistochemistry (observation of effects on lesion cavity, vessels and axon growth). Functional Outcome Measures: Terminal Electrophysiology (observation of effects on muscle activity). Behavioral Outcome Measures: Weekly plethysmographic assessment (observe the effect on breathing patterns (respiratory rate, respiratory volume, m...

Embodiment 2

[0105] Effects of NPC and E4ORF1+EC transplantation in spinal cord injury model

[0106] Figure 1 provides a schematic representation of the methods and timeline used in the experiments described. Figure 1A. Neural progenitor cells (NPCs) were isolated from the developing rat spinal cord, cultured, frozen and thawed 1 day before transplantation. Figure 1B, Mouse spinal cord endothelial cells (EC) expressing E4ORF1 were thawed and cultured with lenti-GFP virus before transplantation. Figure 1C, 1 week after spinal cord contusion, NPCs and ECs were transplanted into the center of the lesion at a ratio of 1:1 (1,000,000 cells in total). Efficacy of this transplantation model was evaluated using a battery of anatomical (anterograde and retrograde tracers) and functional (terminal septal electromyography, dEMG) assessments. The experimental timeline is shown in Figure 1D.

[0107] Phenotypic analysis of transplanted NPCs and ECs showed differentiation into GFAP-positive glial ...

Embodiment 3

[0113] The role of glial progenitor cells or glial cells combined with E4ORF1+EC transplantation in spinal cord injury models

[0114] As described in Example 2, we found that after NPC transplantation, NPC differentiated into GFAP-positive glial cells about 6 weeks after transplantation. Therefore, we hypothesized that if glial progenitor cells or glial cells (instead of NPCs) were transplanted together with E4ORF1+ ECs, the above SCI repair could also be achieved.

[0115] To test this hypothesis, the following experiments were performed and all methods were as described above unless otherwise stated.

[0116] Glial progenitor cells and / or glial cells are obtained. Spinal cord endothelial cells (EC) were obtained and transformed to produce E4ORF1+EC as described above. The first combination of glial progenitor cells and E4ORF1+ECs and the second combination of glial cells and E4ORF1+ECs were transplanted into the center of the lesion in the above SCI model. Efficacy of ...

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Abstract

The present invention provides methods for treating spinal cord injury (SCI). Such methods involve administering E40RF1+ endothelial cells and neural cells (such as neural progenitor cells (NPCs), glial progenitor cells, or glial cells) to subjects having a SCI. The present invention also provides compositions useful in such methods, such as compositions comprising E40RF1+ endothelial cells and / orneural cells (such as NPCs, glial progenitor cells, or glial cells).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 620,269, filed January 22, 2018. [0003] incorporated by reference [0004] The text of all documents cited herein are incorporated by reference in their entirety for purposes of jurisdictions that permit incorporation by reference only. Furthermore, any manufacturer's instructions or catalogs for any products cited or mentioned herein are hereby incorporated by reference. Documents incorporated herein by reference or any teachings therein may be used in the practice of the present invention. Many of the teachings of U.S. Patent No. 8,465,732, entitled "Endothelial cells expressing adenovirus E4ORF1 and methods of use thereof," may be used in conjunction with or adapted to the present invention used with the present invention. Accordingly, the entire contents of US Patent No. 8,465,732 are hereby expressly incorporated by reference into thi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/30A61K35/12A61P25/00A61P19/08
CPCA61K35/30A61K35/44A61K48/00C12N5/0618A61L27/3808A61L27/383A61L27/3878A61L27/3886A61L2400/06C12N2740/16043A61P25/00A61K35/76A61K38/162
Inventor D·J·诺兰M·A·莱恩L·强L·V·若卢杰夫瓦
Owner ANGIOCRINE BIOSCI