Long-term clinical and safety outcomes from a single-site phase 1 study of neural stem cell transplantation for chronic thoracic spinal cord injury

Abstract

We report the long-term results for a phase 1 study of neural stem cell transplantation for chronic spinal cord injury. The trial was registered on ClinicalTrials.gov as NCT01772810. The primary outcome of the trial was to test the feasibility and safety of human spinal cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury in four subjects with thoracic two to thoracic twelve spinal cord injury. Here, we report that all four subjects tolerated the stem cell implantation procedure well, and two subjects had durable electromyography-quantifiable evidence of neurological improvement as well as increased neurological motor and sensory scores at five years post-transplantation.

Keywords: SCI; clinical trial; neural stem cell therapy; neurosurgery; regenerative medicine; spinal cord injury; spinal surgery; stem cells.

Graphical abstract

Figure 1

Eligibility screening, patient selection, intra-operative procedure, follow-up, and advantages noted from this study †See Curtis et al. for complete screening criteria.

Figure 2

ISNCSCI exam scores from screening to 60 months reveals (A and B) a one level improvement in NLI for subject 001 and 010 and remained stable for subjects 006 and 008; (C and D) average motor and sensory scores improved one level in subject 001 and 1.5 levels in subject 010; (E and F) zone of partial preservation motor remains stable across all 4 subjects, and sensory improved 1–2 levels in all 4 patients.

Figure 3

Pain and spinal cord independence trends from screening to month 60 (A) Change from baseline pain scores reveals improved pain scores in 2 patients, stable pain score in 1 patient, and increased pain in 1 patient. (B) Spinal cord independence measure remained mostly stable to mildly decreased in 3 patients but significantly decreased in 1 patient.

Figure 4

MRI cervical-thoracic T2 sagittal and AvDC sagittal sequences (A) Subject 001 at 60 months (T2) and 18 months (AvDC) post-transplant (myelomalacia is seen at the area of SCI with no extension of myelomalacia or syringomyelia post-transplant), (B) subject 006 at 60 months (T2) and 30 months (AvDC) post-transplant, (C) subject 008 at 24 months (T2, AvDC) post-transplant, and (D) subject 010 at 24 months (T2, AvDC) post-transplant. In all four patients, T2 and AvDC imaging revealed a stable appearance of the spinal cord both at the injury site and rostral/caudal to the injury site.

Figure 5

BMCA to identify voluntary or reinforcement maneuver-initiated EMG activity (A and B) Recording of voluntary or reinforcement maneuver-triggered BMCA activity showed no detectable BMCA responses at 18 months after cell transplantation in subject 006. (C and D) Subsequent recording performed at 60 months after transplantation showed suggestion of volitional EMG response in tibialis anterior (C) and after a reinforcement maneuver (D). Red arrowheads show new activity in tibialis anterior with volitional bilateral hip flexion command and reinforcement maneuver (neck flexion and deep breath). The horizontal black bar indicates onset marker. (E and F) No detectable BMCA volitional or reinforcement maneuver response was observed at 18 months in subject 010. (G and H) Recording at 42 months suggests new EMG activity in medial hamstring with reinforcement maneuver (H) but not with volitional command (G).