TY - JOUR
T1 - Targeted spinal cord therapeutics delivery
T2 - Stabilized platform and microelectrode recording guidance validation
AU - Riley, Jonathan
AU - Butler, John
AU - Baker, Kenneth B.
AU - McClelland, Shearwood
AU - Teng, Qingshan
AU - Yang, Jun
AU - Garrity-Moses, Mary
AU - Federici, Thais
AU - Boulis, Nicholas M.
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
KW - Intraspinal targeting
KW - Microelectrode recording
KW - Microinjection platform
KW - Molecular therapeutics
KW - Therapeutics delivery
UR - http://www.scopus.com/inward/record.url?scp=40349108785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40349108785&partnerID=8YFLogxK
U2 - 10.1159/000112426
DO - 10.1159/000112426
M3 - Article
C2 - 18073518
AN - SCOPUS:40349108785
SN - 1011-6125
VL - 86
SP - 67
EP - 74
JO - Stereotactic and Functional Neurosurgery
JF - Stereotactic and Functional Neurosurgery
IS - 2
ER -