TRANSPLANTATION OF AUTOLOGOUS OLFACTORY ENSHEATHING CELLS IN SPINAL CORD INJURY: SURGERY AND TWELVE MONTH SAFETY DATA OF A PHASE ONE HUMAN CLINICAL TRIAL

Abstract

Introduction The devastating and permanent effects of complete spinal cord injury are well documented. In animal models, olfactory ensheathing cells (OEC) transplanted into areas of complete spinal cord injury have promoted regeneration of the neural elements with reconnection of the descending motor pathways. This reproducible anatomical finding is associated with significant motor functional recovery. Accordingly, cellular transplantation therapies have been advocated for human spinal cord injury.

In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the spinal cord of three humans with complete spinal cord injury. This paper describes the trial and the surgical procedures and presents twelve month safety data.

Methods Six patients with paraplegia resulting from chronic (6 – 36 months post-injury) traumatic spinal cord injury (thoracic) were enrolled in the trial. Exclusion criteria included the presence of vertebral column instability, syringomyelia, an implanted spinal device or instrumentation and the presence of psychological instability. The patients were allocated to a treatment group and a control group. No intervention was undertaken to the control group.

Olfactory ensheathing cells were harvested from each subject in the surgery group, grown and purified in vitro. After exposure via laminectomy, durotomy and adhesolysis, the cells were injected into the region of injured spinal cord.

All patients are tested on enrollment and then at regular intervals up to three years by a group of assessors who are blinded to the treatment or control group status. These assessments include physical, radiological, neurophysiological and psychosocial parameters.

Results All surgery patients exhibited continuity of presumed pia through the cystic region at the site of injury. The spinal cord adjacent to the cyst appeared macroscopically normal. There were no complications of surgery evident in the peri-operative period. At twelve months there was no evidence of tumour formation, syrinx development, clinical or psychosocial deterioration.

Discussion The dictum, primum non nocere, is especially relevant to the emerging field of human spinal cord regeneration. Animal models promise such exciting potentials for therapy in this devastating condition, that the possibilities need to be fully explored. Anecdotal, non-trial based reports suggest that equivalent results may be able to be obtained in humans. However, science and care should guide the endeavours in this controversial field.

This is the first reported trial of OEC’s in human spinal cord injury. Twelve-month data in a small cohort shows that there is no evidence of adverse events that would preclude completion of the current trial and the development of efficacy trials.