Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury

Allan D Levi, Kim D. Anderson, David O. Okonkwo, Paul Park, Thomas N. Bryce, Shekar N. Kurpad, Bizhan Aarabi, Jane Hsieh, Katie Gant

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)891-902
Number of pages12
JournalJournal of neurotrauma
Volume36
Issue number6
DOIs
StatePublished - Mar 15 2019

Fingerprint

Neural Stem Cells
Stem Cell Transplantation
Spinal Cord Injuries
Transplants
Transplantation
Safety
Nerve Tissue
Quadriplegia
Syringes
Wounds and Injuries
Tacrolimus
Immunosuppressive Agents
Upper Extremity
Immunosuppression
Spinal Cord
Cohort Studies
Central Nervous System
Magnetic Resonance Imaging
Cervical Cord

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 journalArticle

Levi, AD, Anderson, KD, Okonkwo, DO, Park, P, Bryce, TN, Kurpad, SN, Aarabi, B, Hsieh, J & Gant, K 2019, 'Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury', Journal of neurotrauma, vol. 36, no. 6, pp. 891-902. https://doi.org/10.1089/neu.2018.5843
Levi, Allan D ; Anderson, Kim D. ; Okonkwo, David O. ; Park, Paul ; Bryce, Thomas N. ; Kurpad, Shekar N. ; Aarabi, Bizhan ; Hsieh, Jane ; Gant, Katie. / Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury. In: Journal of neurotrauma. 2019 ; Vol. 36, No. 6. pp. 891-902.
@article{b9af27fcaf284408a19d5eb753bc0910,
title = "Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury",
abstract = "Human neural stem cell transplantation (HuCNS-SC {\circledR} ) 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.",
keywords = "human, SCI, stem cells, tetraplegia, transplantation",
author = "Levi, {Allan D} and Anderson, {Kim D.} and Okonkwo, {David O.} and Paul Park and Bryce, {Thomas N.} and Kurpad, {Shekar N.} and Bizhan Aarabi and Jane Hsieh and Katie Gant",
year = "2019",
month = "3",
day = "15",
doi = "10.1089/neu.2018.5843",
language = "English (US)",
volume = "36",
pages = "891--902",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "6",

}

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 -