Spinal cord injury. From the proof of principle to the therapeutic tool

Spinal cord injury is a devastating pathology with heavy social and personal sequels,. Therapeutic strategies are organized around three research directions: Neuroprotection, axonal regeneration and substitutive therapies. Of particular interest is axonal regeneration. Since it may be applicable to other spinal or brain pathologies. The condition for regeneration in the central nervous system is the control of tissular surrounding after the lesion, and essentially the constitution of a glial scar. A key factor in the glial scar is the massive synthesis of glial fibrous proteins GFAP and Vimentin. We have devised a transgenic mouse model in which the genes coding for these proteins have been inactivated. After a lateral hemisection of the spinal cord, transgenic mice recover within five weeks the function of the paralyzed hind limb and the absence of glial scar formation is correlated with the regeneration of descending serotonergic axons. The same results have been obtained in native mice injected locally with a lentiviral vector carrying a siRNA for GRAP. This tool, which can potentially be used in injured patients, will be tested on a primate model with a non-invasive follow-up with high resolution MRI.