Autologous Bulbar Olfactory Ensheathing Cells and Nerve Grafts for Treatment of Patients With Spinal Cord Transection

The purpose of this experimental therapy is to evaluate the safety and efficacy of transplantation of autologous olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) obtained from the olfactory bulb with simultaneous reconstruction of the posttraumatic spinal cord gap with peripheral nerve grafts, in patients with chronic complete spinal cord injury. The treatment will be performed in two patients that have sustained an anatomically complete spinal cord transection between the spinal cord segments C5 and Th10.

All patients wanting to participate in this study have to send their application at the address:

walk-again-project.org

The "Wrocław Walk Again" project is a continuation of the innovative experimental therapy involving reconstruction of patient's severed spinal cords, using their own olfactory glial cells from the olfactory bulb as well as implants from peripheral nerves. The first operation of its kind was performed in 2012. The reconstruction of the cord was a success: the patient regained partial feeling and volitional mobility in paralysed limbs (Cell Transplantation, Vol. 23, pp. 1631-1655, 2014). The experiment's success provided inspiration to continue with the project in order to assess the safety and effectiveness of the therapy applied. The continuation involves planning to qualify two patients with traumatic spinal cord injury, who will then be given treatment and physiotherapy. The programme will be conducted in Wroclaw, Poland, by an interdisciplinary team of doctors and scientists. The Nicholls Spinal Injury Foundation (UK) will be making a significant contribution to the project. Due to this, participants will not need to pay for their experimental treatment or physiotherapy.

The main goal of the study is to answer the question if there is possible to evoke functional regeneration of severed spinal cord axons after a two-stage surgical intervention in patients sustaining a complete spinal cord transection between the spinal cord segments C5 and Th10. Patients with clinically, electrophysiologically and radiologically features of complete spinal cord injury will undergo an 8-month neurorehabilitation regimen. Patients who will not show electrophysiological and clinical signs of recovery from the spinal cord injury will enter the surgical part of the study.

During the first surgery the patient's own olfactory bulb will be obtained. The human autologous olfactory ensheathing glia and olfactory fibroblast isolated from the olfactory bulb will be used for production of Glial Neuropatch in accordance with the methodology adjusted in grant number GR-797/NCN/2013 and 2012/06/M/NZ4/00138, in a laboratory facility, in accordance with the good manufacture procedures (GMP). The final Product will consist of the aforementioned cell suspension embedded with collagen scaffold. The European Medicines Agency/Committee for Advanced Therapies (EMA/CAT) considers that the Product Glial Neuropatch falls within the definition of a tissue engineered product of an advanced therapy medicinal product (decision EMA/CAT/293903/2018 from 22 June 2018: Scientific recommendation on classification of advanced therapy medicinal products Article 17 - Regulation (EC) No 1394/2007).

The second surgery will consist of laminectomy/laminotomy, midline durotomy above the area of spinal cord lesion, detethering of the spinal cord from fibrous adhesions, resection of the posttraumatic spinal cord glial scar, delivering of cultured OEC/ONFs explants (Glial Neuropatch) to the area of spinal cord injury and finally bridging of the spinal cord gap by harvested autologous sural nerve grafts.

After discharge from the hospital, the patients will be subjected to a minimum 2-year neurorehabilitation in accordance with the same program as before the operation.

Eligibility Criteria:
Inclusion Criteria:

1. A single spinal cord injury between vertebral levels C5-Th10 with a total anatomic disruption of continuity.
2. Myelopathy not exceeding 2 spinal cord segments as confirmed by MRI.
3. Complete loss of sensory and motor function below the injury, confirmed in serial control clinical studies (ASIA Category A) and neurophysiological studies (MEP, SSR, EPT, EMG, ENG, von Frey's filaments)
4. Age from 16 to 65 years.
5. Patient undergoing continuous rehabilitation.
6. Good patient motivation and cooperation, no mental disturbances.
7. Patient is ready to stay with an accompanying person for at least 3 years in Poland.
8. Patient without cardiac disease and without epilepsy, does not have peacemaker or any electronic or ferromagnetic implants.

Exclusion Criteria:

1. A coexisting lesion of the nervous system.
2. Progressive post-traumatic syringomyelia.
3. Significant spinal stenosis or instability.
4. Muscle atrophy or joint ossifications.
5. Severe systemic disease such as neoplasm, contagious disease, diabetes etc.
6. Chronic sinusitis destroying the paranasal sinuses, tumors of nasal cavities or patients with hyposmia in repetitive smell perception tests will be excluded.
7. Implants or the health status described in point 8 (see above).

Note: All patients wanting to participate in this study have to send their application via the walk-again-project.org recruitment website!