Fatiha Nothias, Neuroscience Paris Seine, University P. & M. Curie, Paris, France

Combined strategy for spinal cord repair - a neuroprotective molecule linked to a bioactive hydrogel

Funded in: 2014, 2015, 2016

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Problem: After SCI, cystic cavities are formed and are surrounded by a glial scar inhibiting axonal regrowth.
Target: Neuroprotective and neurorestaurative effects of a chitosan-based hydrogel loaded with a synthetic molecule
Goal: Successful restoration of the damaged tissue and promotion of remyelination and fiber regrowth through the lesion site.

In mammals, spinal cord injury (SCI) provokes cellular and molecular changes that lead to the formation of cystic cavities surrounded by a glial scar. This constitutes a physical and chemical barrier to spontaneous axon regeneration, which is even further inhibited by myelin degradation products. In addition, ischemia and inflammation resulting from breakdown of the blood-spinal cord barrier contribute to secondary damage and neurological deficits.
Novel biomaterials offer a particularly promising perspective for new therapeutic approaches to tissue repair. Implanted into the SCI, such biomaterials may function both as extracellular matrix substitute, and as bioactive scaffold structure. Accordingly, Dr. Nothias’ team has associated its experience on traumatic SCI with that of the group of physico-chemists headed by Laurent David (IMP, University Claude Bernard, Lyon 1) to develop a new therapeutic strategy for SCI repair. Preliminary data clearly show that implantation of a physically and chemically well characterized hydrogel into SCI provides a favorable environment for successful restoration of the damaged tissue by reducing scar formation, and allowing for fiber regrowth and revascularization through the lesion site.

In view of further optimization, it will be investigated whether the therapeutic potential of the hydrogel implant strategy can be enhanced by administration of a synthetic molecule reported to have neuroprotective effects, and to promote differentiation of myelinating cells.

Different groups of experimental animal models will be used to analyze:

  • The potential of functional recovery
  • Anatomical/histological parameters such as vascularization, inflammation, glial scar fomation, and particularly, distance of fiber outgrowth, and level of remyelination.

Based on longstanding experience of a pluridisciplinary consortium and strong preliminary data, this project will allow for a quantitative evaluation of the concept of a combined strategy for spinal cord repair.