Phase 1 Safety Trial of Autologous Human Schwann Cell Transplantation in Chronic Spinal Cord Injury

Abstract

A phase 1 open-label, non-randomized clinical trial was conducted to determine feasibility and safety of autologous human Schwann cell (ahSC) transplantation accompanied by rehabilitation in participants with chronic spinal cord injury (SCI). Magnetic resonance imaging (MRI) was used to screen eligible participants to estimate an individualized volume of cell suspension to be implanted. The trial incorporated standardized multi-modal rehabilitation before and after cell delivery. Participants underwent sural nerve harvest, and ahSCs were isolated and propagated in culture. The dose of culture-expanded ahSCs injected into the chronic spinal cord lesion of each individual followed a cavity-filling volume approach. Primary outcome measures for safety and trend-toward efficacy were assessed. Two participants with American Spinal Injury Association Impairment Scale (AIS) A and two participants with incomplete chronic SCI (AIS B, C) were each enrolled in cervical and thoracic SCI cohorts (n = 8 total). All participants completed the study per protocol, and no serious adverse events related to sural nerve harvest or ahSC transplantation were reported. Urinary tract infections and skin abrasions were the most common adverse events reported. One participant experienced a 4-point improvement in motor function, a 6-point improvement in sensory function, and a 1-level improvement in neurological level of injury. Follow-up MRI in the cervical (6 months) and thoracic (24 months) cohorts revealed a reduction in cyst volume after transplantation with reduced effect over time. This phase 1 trial demonstrated the feasibility and safety of ahSC transplantation combined with a multi-modal rehabilitation protocol for participants with chronic SCI.

Keywords: Schwann cells; autologous transplantation; chronic; human; paraplegia; spinal cord injury.

FIG. 1.

Study design and timeline of interventions.

FIG. 2.

Illustration (A-E) showing pial opening (blue arrow), placement of tubing into injured cavity, injection of autologous human Schwann cells (ahSC; green) and closure of pial opening. Intraoperative view (right) with the surgical microscope showing insertion of tubing (black arrow) into the chronic cyst cavity for injection of ahSC.

FIG. 3.

Serial sagittal magnetic resonance images for the cervical (A) and thoracic (B) cohort showing changes in spinal cord cyst geometry before and after autologous human Schwann cell transplantation.

FIG. 4.

(A) Mean (± standard deviation) change in spinal cord cyst volume calculated from MR images for the cervical and thoracic chronic spinal cord injury cohort after autologous human Schwann cells transplantation; (B) The volume of the spinal cord cavities estimated from serial magnetic resonance imaging is shown (PT: post-transplant). Cervical cavities are indicated as triangles and thoracic cavities as circles. The average volume of thoracic cavities was smaller. In 6/8 participants an initial cavity volume reduction was observed that averaged 34.3 ± 12.1%.

FIG. 5.

Adverse event profile by type and participant.

FIG. 6.

Pain diagrams for four participants who experienced chronic pain at Baseline, and the T1 (1 month), T2 (6 month), T3 (12 month), and T4 (2 year) time-points.