648. Lentiviral Vector Expressing Retinoic Acid Receptor |[beta]|2 Promotes Regeneration in a Rat Spinal Cord Injury Model

Top of pageAbstract After spinal cord injury, axons in the central nervous system (CNS) fail to regenerate resulting in paralysis. The factors that contribute to this regenerative failure include the inihibitory environment at the injury site as well as the intrinsic growth potential of injured axons. Previously we have demonstrated that retinoic acid receptor |[beta]|2 (RAR|[beta]|2), a transcription factor activated by retinoic acid, can induce neurite outgrowth in adult spinal cord explants and promote functional regeneration in a rat model of cervical rhizotomy. Here we investigate the utility of a minimal equine infectious anaemia virus (EIAV)-based lentiviral vector expressing RAR|[beta]|2 in stimulating axonal outgrowth in a rat spinal cord injury model. EIAV-RAR|[beta]|2 was injected into the sensorimotor cortex prior to lesioning of dorsal columns in the cervical cord. At 4 weeks after lesion, RAR|[beta]|2-treated animals demonstrated regeneration of descending corticospinal axons up to, and beyond the lesion site, compared to control animals that received an EIAV vector expressing |[beta]|-galactosidase. These anatomical observations correlated to an improvement in task performance in locomotor and proprioceptive behavioural tests as well as an increase in post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons. This suggests that lentiviral-mediated delivery of RAR|[beta]|2 promoted functional regeneration of CNS axons in the injured spinal cord and may thus be exploited as a novel approach to therapeutic applications in the treatment of spinal cord injuries.