Targeted spinal cord therapeutics delivery: Stabilized platform and microelectrode recording guidance validation

Jonathan Riley, John Butler, Kenneth B. Baker, Shearwood McClelland, Qingshan Teng, Jun Yang, Mary Garrity-Moses, Thais Federici, Nicholas M. Boulis

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Background/Aims: No validated delivery technique exists for accurate, reproducible delivery of biological therapies to discrete spinal cord targets. To address this unmet need, we have constructed a stabilized platform capable of supporting physiologic mapping, through microelectrode recording, and cellular or viral payload delivery to the ventral horn. Methods: A porcine animal model (n = 7) has been chosen based upon the inherent morphologic similarities between the human and porcine spine. Animals underwent physiologic mapping and subsequent microinjection of a green-fluorescent-protein-labeled cell suspension. Sacrifice (t = 3 h) was performed immediately following behavioral assessment. Results: Histologic analysis has supported our ability to achieve localization to the ipsilateral ventral horn in the spinal cord. Complications included death due to malignant hyperthermia (n = 1), hindlimb dysfunction attributable to epidural hematoma (n = 1), and hindlimb dysfunction attributable to cord penetration (n = 2). Conclusions: These results indicate an ability to achieve accurate targeting, but the elevated incidence of neurologic morbidity will require further studies with longer follow-ups that incorporate procedural and equipment modifications that will allow for a reduced number of cord penetrations and will account for observed cardiorespiratory-associated cord movement. These initial results reinforce the challenges of translating biological restorative therapies from small to large animal models and ultimately to humans.

Original languageEnglish (US)
Pages (from-to)67-74
Number of pages8
JournalStereotactic and Functional Neurosurgery
Volume86
Issue number2
DOIs
StatePublished - Mar 1 2008

Keywords

  • Intraspinal targeting
  • Microelectrode recording
  • Microinjection platform
  • Molecular therapeutics
  • Therapeutics delivery

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    Riley, J., Butler, J., Baker, K. B., McClelland, S., Teng, Q., Yang, J., Garrity-Moses, M., Federici, T., & Boulis, N. M. (2008). Targeted spinal cord therapeutics delivery: Stabilized platform and microelectrode recording guidance validation. Stereotactic and Functional Neurosurgery, 86(2), 67-74. https://doi.org/10.1159/000112426