Name: surgical technique for spinal cord delivery of therapies: demonstration of procedure in gottingen minipigs
Uploaded: 2012-12-07T12:00:00
Description: Watch this Scientific Journal Video about Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs at JoVE.com

We thank the Emory University Division of Animal Resources staff for veterinary care. Funding sources include: ALS Association, Department of Defense, and Neuralstem, Inc.

1. Animal Use
Procedures demonstrated herein have been approved by the Emory University Institutional Animal Care and Use Committee (IACUC). Female Gottingen minipigs weighing approximately 15-20 kg are used.
2. Anesthesia
Animals are fasted approximately 12 hr prior to surgery. Animal sedation and anesthesia induction consist of a cocktail of intramuscular Ketamine (35 mg/kg), Acepromazine (1.1 mg/kg), and Atropine (0.04 mg/kg). Animals are ...

<ol>
	<li>Usvald, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+dosing+regimen+and+reproducibility+of+intraspinal+grafting+of+human+spinal+stem+cells+in+immunosuppressed+minipigs.">Analysis of dosing regimen and reproducibility of intraspinal grafting of human spinal stem cells in immunosuppressed minipigs.</a> Cell Transplant. 19, 1103-1122 (2010).</li><li>Riley, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Targeted+spinal+cord+therapeutics+delivery:+stabilized+platform+and+microelectrode+recording+guidance+validation.">Targeted spinal cord therapeutics delivery: stabilized platform and microelectrode recording guidance validation.</a> Stereotact. Funct. Neurosurg. 86, 67-74 (2008).</li><li>Federici, T., Riley, J., Park, J., Bain, M., Boulis, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preclinical+safety+validation+of+a+stabilized+viral+vector+direct+injection+approach+to+the+cervical+spinal+cord.">Preclinical safety validation of a stabilized viral vector direct injection approach to the cervical spinal cord.</a> Clin. Transl. Sci. 2, 165-167 (2009).</li><li>Riley, J. P., Raore, B., Taub, J. S., Federici, T., Boulis, N. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Platform+and+Cannula+Design+Improvements+for+Spinal+Cord+Therapeutics+Delivery.">Platform and Cannula Design Improvements for Spinal Cord Therapeutics Delivery.</a> Neurosurgery. 69, 147-154 (2011).</li><li>Riley, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cervical+spinal+cord+therapeutics+delivery:+preclinical+safety+validation+of+a+stabilized+microinjection+platform.">Cervical spinal cord therapeutics delivery: preclinical safety validation of a stabilized microinjection platform.</a> Neurosurgery. 65, 754-761 (2009).</li><li>Raore, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cervical+multilevel+intraspinal+stem+cell+therapy:+assessment+of+surgical+risks+in+Gottingen+minipigs.">Cervical multilevel intraspinal stem cell therapy: assessment of surgical risks in Gottingen minipigs.</a> Spine. 36, 164-171 (2011).</li><li>Boulis, N. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Translational+stem+cell+therapy+for+amyotrophic+lateral+sclerosis.">Translational stem cell therapy for amyotrophic lateral sclerosis.</a> Nat. Rev. Neurol. , (2011).</li><li>Riley, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraspinal+Stem+Cell+Transplantation+in+ALS:+A+Phase+I+Safety+Trial,+Technical+Note+&#38;+Interim+Safety+Outcomes.">Intraspinal Stem Cell Transplantation in ALS: A Phase I Safety Trial, Technical Note &#38; Interim Safety Outcomes.</a> Neurosurgery. 71 (2), 405-416 (2012).</li><li>Boulis, N. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lumbar+intraspinal+injection+of+neural+stem+cells+in+patients+with+ALS:+results+of+a+Phase+I+trial+in+12+patients.">Lumbar intraspinal injection of neural stem cells in patients with ALS: results of a Phase I trial in 12 patients.</a> Stem Cells. 30 (6), 1144-1151 (2012).</li></ol>

Despite approval to proceed with the described technique in humans 7-9, critical questions remain to be answered in order for spinal cord therapies to succeed. A rigorous understanding of spinal cord tolerance to intraparenchymal injection is required to enable the planning and execution of trials developing therapies for demyelinating, degenerative, and traumatic spinal cord disease. Currently, there is no clear understanding of the number of injections that the large mammalian spinal cord can...

<table border="1">
 <tbody>
 <tr>
 <td>Name of the equipment</td>
 <td>Company</td>
 <td>Catalogue number</td>
 <td>Comments (optional)</td>
 </tr>
 <tr>
 <td>Spinal Derrick </td>
 <td>Neuralstem, Inc.</td>
 <td></td>
 <td>Neuralstem, Inc. has purchased an exclusive license to this technology </td>
 </tr>
 <tr>
 <td>MINJ-PD Microinjector pump</td>
 <td>Tritech Research, Inc. </td>
 <td></td>
 <td>Customized for this specific application </td>
 </tr>
 <tr>
 <td>Floating Cannula</td>
 <td>Neuralstem, Inc.</td>
 <td></td>
 <td>Custom-designed for this specific application</td>
 </tr>
 </tbody>
</table>

surgical technique for spinal cord delivery of therapies: demonstration of procedure in gottingen minipigs

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use. The size, anatomy, and general vulnerability of the spine and spinal cord of the swine are recognized to better model the human. Moreover, the surgical process of exposing and manipulating the spinal cord as well as closing the wound in the pig is virtually indistinguishable from the human. We believe that the healthy pig model represents a critical first step in the study of procedural safety.

<table border="1">
	<tbody>
		<tr>
			<td colspan="2">Tarlov Score</td>
		</tr>
		<tr>
			<td>0</td>
			<td>Paralysis, no movement</td>
		</tr>
		<tr>
			<td>1</td>
			<td>Perceptible tonus in the hind limbs, slight movement</td>
		</tr>
		<tr>
			<td>2</td>
			<td>Movement in the hind limbs, but unable to sit or stand</td>
		</tr>
		<tr>
			<td>3</td>
			<td>Ability to stand and walk but ataxic and for short periods</td>
		</tr>
		<tr>
			<td>4</td>
			<td>Com...

Watch this Scientific Journal Video about Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs at JoVE.com

Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs

Short visual description of the surgical technique and device used for the delivery of (gene and cell) therapies into the spinal cord. The technique is demonstrated in the animal but is entirely translatable and currently being used for human application.

This is a  compact visual description of a combination of surgical technique and device  for the  delivery of (gene and cell) therapies into the spinal ...

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