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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - SC0806 (Regenerative treatment of complete Traumatic Spinal Cord injury with a surgical implantation of a biodegradable device with FGF1 and nerve grafts)

Teaser

Summary

The global annual incidence of Spinal Cord Injury (SCI) has been estimated to 22 per million, with approximately 2.5 million survivors living with paralysis. The incidence ranges between 12.7 and 44.3 per million inhabitants depending on country (1). The victims are usually young people. The injury has little effect on life expectancy but leads to enormous challenges to maintain an acceptable quality of life. Forty percent (40%) of all cases have a complete Spinal Cord Injury (2). Following complete injury, the patient faces a permanent loss of function below the site of injury, with devastating consequences for the patientâ€™s quality of life. The cost for society today for Spinal Cord Injury patients is huge. The estimated lifetime cost is approximately 2.5 MEURO for one patient (3).

The overall objective of the project is to perform a clinical trial of a novel regenerative treatment of complete Spinal Cord Injury. Today there is no efficacious treatment for these patients.
The trial is an open, randomized, rehabilitation-controlled study, to assess safety, tolerability, and efficacy, of heparin-activated recombinant human fibroblast growth factor 1 (FGF1), on a biodegradable device, in subjects with traumatic spinal cord injury.

(1) Datamonitor, Stakeholder Opinions: Spinal Cord Injury, 2010.
(2) NSCISC Annual Statistics report 2010.
(3) Krueger et al., 2013.

Work performed

The clinical study on the regenerative treatment of patients with complete spinal cord injury has successfully started. In total nineteen patients from Sweden have been evaluated, of which eight matched the inclusion criteria and have been randomised into the study. Of the eight patients included in the study, five were randomised to surgery and rehabilitation, and three to rehabilitation control. Control subjects receive physiotherapy training only. As an integral part in the project, the patients receive physiotherapy training for up to 18 months. The specific walking training uses a robotic system that enables intensive functional locomotion therapy. In line with the project plan, the investment, delivery and installation of a Lokomat walking training robotic system, has successfully been performed at Rehabilitation Station Stockholm (RSS) in Sweden. The first safety interim analysis was conducted in Q2 2017 by an independent Data Monitoring Committee, that stated that the study may continue according to plan. As of the end of the second reporting period, all eight patients were actively engaged in the planned rehabilitation training program with one hour sessions, three times/week. The project has successfully incorporated new partners and clinics in Norway and Estonia into the consortium, to replace the Danish partners who left. The project consortium now includes partners in Sweden, Finland, Norway and Estonia. So far, Sweden has recruited all the patients included in the study. Three sites are now being added to the study to ensure good patient availability of eligible patients (FI, NO, EE). Ethics Committee approvals in Norway, Estonia and Finland were achieved and the Estonian Health Authorities have approved the clinical trial application. Work is ongoing with the clinical trial applications in Norway and Finland.

Final results

Current state-of-the-art: Spinal Cord Injury causes degeneration of the white matter distal to the site of injury. Subsequently the axon fails to regenerate across the Spinal Cord Injury because of the local inflammatory environment in the spinal cord. This inflammatory reaction causes glial proliferation, migration and the local release of several pro-inflammatory cytokines resulting in an astroglial scar. In addition, several local factors that prevent the regeneration of nerves in the CNS have been identified to be excessively released. As a result, complete SCI leads to permanent loss of neurological function. Today, no regenerative treatment method, feasible for clinical practice, exists for complete SCI. To the best of our knowledge, BioArctic is pioneering this segment of unmet medical need. BioArctic holds patents covering the device and the treatment method. Other companies focus on developing therapies for a different group of patients with partial sensory functions retained as a result of partial (incomplete) SCI.

Progress beyond state-of the art: The treatment method developed by BioArctic utilises the ability of central nerves to grow in transplanted grafts of peripheral nerves that shield the regenerating nerves from the local inflammatory environment at the site of injury. Several peripheral nerve grafts are transplanted into the biodegradable device that acts as support for guided nerve regeneration between the upper and lower portion of the damaged spinal cord. The strategy is based on the use of a device with channels for the peripheral nerve grafts. The entrance and exit holes in the device have been localized for optimal coupling between descending motor tracts and motor neuron pools as well as for the ascending sensory system and sensory neuron pools. This design supports and guides regenerative connection between white and grey matter in the spinal cord. The device allows for nerve graft positioning with high precision during surgery. The device is biodegradable and biocompatible, leaving no traces in the healed injured area wound, thus avoiding the risk for long-term potential problems with non-degradable implants. To further stimulate nerve generation the device is loaded with the growth factor FGF1, which is slowly released as the device is degraded. FGF1 is a well characterized growth factor present in neurons and involved in nerve regeneration and healing. The combination of FGF1 and peripheral nerve grafts creates a favorable environment for axon regeneration. It is known that heparin binds and activates FGF1. Hence, to achieve full activity, FGF1 is formulated with heparin. The device containing heparin-activated FGF1 is used during the neurosurgical procedure, to replace injured tissue and to connect viable nerves to the other side of the injured segment.

Expected potential impact and advancement: The project is expected to translate our preclinical discoveries, offering a new regenerative treatment of complete SCI, into an effective therapy in clinics, where it may restore lost function to potentially thousands of SCI patients worldwide. The treatment concept holds the potential for significantly improving quality of life of many patients, and also to improve the competitiveness of BioArctic as a small/medium sized enterprise (SME) committed to developing and delivering efficient regenerative therapies to patients, and to the European and world markets.