Abstract
Human neural stem cell transplantation (HuCNS-SC ® ) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 891-902 |
| Number of pages | 12 |
| Journal | Journal of neurotrauma |
| Volume | 36 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 15 2019 |
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Keywords
- human
- SCI
- stem cells
- tetraplegia
- transplantation
ASJC Scopus subject areas
- Clinical Neurology
Cite this
Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury. / Levi, Allan D; Anderson, Kim D.; Okonkwo, David O.; Park, Paul; Bryce, Thomas N.; Kurpad, Shekar N.; Aarabi, Bizhan; Hsieh, Jane; Gant, Katie.
In: Journal of neurotrauma, Vol. 36, No. 6, 15.03.2019, p. 891-902.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury
AU - Levi, Allan D
AU - Anderson, Kim D.
AU - Okonkwo, David O.
AU - Park, Paul
AU - Bryce, Thomas N.
AU - Kurpad, Shekar N.
AU - Aarabi, Bizhan
AU - Hsieh, Jane
AU - Gant, Katie
PY - 2019/3/15
Y1 - 2019/3/15
N2 - Human neural stem cell transplantation (HuCNS-SC ® ) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.
AB - Human neural stem cell transplantation (HuCNS-SC ® ) is a promising central nervous system (CNS) tissue repair strategy in patients with stable neurological deficits from chronic spinal cord injury (SCI). These immature human neural cells have been demonstrated to survive when transplanted in vivo, extend neural processes, form synaptic contacts, and improve functional outcomes after experimental SCI. A phase II single blind, randomized proof-of-concept study of the safety and efficacy of HuCNS-SC transplantation into the cervical spinal cord was undertaken in patients with chronic C5-7 tetraplegia, 4-24 months post-injury. In Cohort I (n = 6) dose escalation from 15,000,000 to 40,000,000 cells was performed to determine the optimum dose. In Cohort II an additional six participants were transplanted at target dose (40,000,000) and compared with four untreated controls. Within the transplant group, there were nine American Spinal Injury Association Impairment Scale (AIS) B and three AIS A participants with a median age at transplant of 28 years with an average time to transplant post-injury of 1 year. Immunosuppression was continued for 6 months post-transplant, and immunosuppressive blood levels of tacrolimus were achieved and well tolerated. At 1 year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on magnetic resonance (MR) imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohorts I and II demonstrated a trend toward Upper Extremity Motor Score (UEMS) and Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) motor gains in the treated participants, but at a magnitude below the required clinical efficacy threshold set by the sponsor to support further development resulting in early study termination.
KW - human
KW - SCI
KW - stem cells
KW - tetraplegia
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=85062424708&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062424708&partnerID=8YFLogxK
U2 - 10.1089/neu.2018.5843
DO - 10.1089/neu.2018.5843
M3 - Article
C2 - 30180779
AN - SCOPUS:85062424708
VL - 36
SP - 891
EP - 902
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
SN - 0897-7151
IS - 6
ER -