Indexed on: 06 Sep '18Published on: 06 Sep '18Published in: Journal of neurotrauma
Human neural stem cell transplantation (HuCNS-SC) is a promising CNS tissue repair strategy in patients suffering from 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 M to 40 M cells was performed to determine the optimum dose. In Cohort II an additional 6 participants were transplanted at target dose (40 M) and compared to 4 non-treated controls. Within the transplant group, there were 9 AIS B and 3 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 one year post-transplantation, there was no evidence of additional spinal cord damage, new lesions, or syrinx formation on MR imaging. In summary, the incremental dose escalation design established surgical safety, tolerability, and feasibility in Cohort I. Interim analysis of Cohort I and II demonstrated a trend towards UEMS and 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.