Lentiviral Vector Expressiing Retinoic Acid Receptor Beta 2 promotes Regeneration in a rat spinal cord injury model

After spinal cord injury, axons in the central nervous system(CNS) fail to regenerate resulting in paralysis. The factors thatcontribute to this regenerative failure include the inihibitoryenvironment at the injury site as well as the intrinsic growth potentialof injured axons. Previously we have demonstrated that retinoicacid receptor β2 (RAR), a transcription factor activated by retinoicacid, can induce neurite outgrowth in adult spinal cord explants andpromote functional regeneration in a rat model of cervical rhizotomy.Here we investigate the utility of a minimal equine infectious anaemiavirus (EIAV)-based lentiviral vector expressing RARβ2 in stimulatingaxonal outgrowth in a rat spinal cord injury model. EIAV-RARβ2 was injected into the sensorimotor cortex prior to lesioning of dorsalcolumns in the cervical cord. At 4 weeks after lesion, RAR
β2-treatedanimals demonstrated regeneration of descending corticospinal axonsup to, and beyond the lesion site, compared to control animals thatreceived an EIAV vector expressingβ-galactosidase. Theseanatomical observations correlated to an improvement in task performance in locomotor and proprioceptive behavioural tests aswell as an increase in post-synaptic activity below the lesion afterelectrical stimulation of corticospinal neurons. This suggests thatlentiviral-mediated delivery of RARβ2 promoted functionalregeneration of CNS axons in the injured spinal cord and may thusbe exploited as a novel approach to therapeutic applications in thetreatment of spinal cord injuries.