Repairing the Spinal Cord with a Sequential Treatment Combining Cell Therapy and Neurosteroid

We first demonstrated that nasal olfactory ensheathing cells, transplanted in rodent lesioned spinal cord, efficiently promoted locomotor and electrophysiological recovery. We then performed the first clinical trial based on the autologous transplantation of olfactory ensheathing cells into the spinal cord of 6 patients with complete, thoracic paraplegia. In one transplant recipient (out of three), there was an improvement over 3 segments in light touch and pin-prick sensitivity. In our clinical design, we opted for a six month-delayed transplantation. However, parallel studies, based on the grafting of bone marrow cells or activated macrophages in paraplegic patients, indicate that improvement is only observed when cell therapy occurs during the acute or sub-acute phases. It is therefore critical to treat the injured individuals as soon as possible. As a result, we devised a method for speeding up the culture process in order to raise billions of cells within a time frame of 2 to 3 weeks and we searched for a "wait a while" molecule that displays neuroprotective and neurotrophic properties, namely cholecalciferol (vitamin D3). In a first study, using a rat model of spinal cord compression, we observed that vitamin D-treated rats displayed, three months after injury, a significant improvement of ventilatory frequency and a reduction of H reflex indicating functional improvements, at three months post-injury. In a second study, we used a rat model of cervical hemisection (C2) and demonstrated an improved locomotor recovery and a significantly higher rate of axons crossing the lesion site in treated animals. We are now planning a phase II multicentric clinical trial assessing the efficacy of cholecalciferol in patients with a cervical trauma. The cohort will include 30 patients with a complete injury. Patients will be treated for one year, from Day 1 post-injury, with decreasing doses of cholecalciferol. The primary outcome will be the improvement of the Upper-Extremity Motor Score (UEMS) recovery. Secondary outcome measures will include sensory index scores, spasticity, pain and quality of life.