Faculty Collaboration Database

Clinical Outcomes from a Multi-Center Study of Human Neural Stem Cell Transplantation in Chronic Cervical Spinal Cord Injury. J Neurotrauma 2019 Mar 19;36(6):891-902

Date

09/06/2018

Pubmed ID

30180779

DOI

10.1089/neu.2018.5843

Scopus ID

2-s2.0-85062424708 (requires institutional sign-in at Scopus site)   102 Citations

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.

Author List

Levi AD, Anderson KD, Okonkwo DO, Park P, Bryce TN, Kurpad SN, Aarabi B, Hsieh J, Gant K

Author

Shekar N. Kurpad MD, PhD Chair, Director, Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Cervical Cord
Humans
Male
Middle Aged
Neural Stem Cells
Proof of Concept Study
Recovery of Function
Single-Blind Method
Spinal Cord Injuries
Stem Cell Transplantation
Young Adult