Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1

Neutralizing the myelin-associated growth inhibitor Nogo-A in adult spinal cord-injured rats can promote regeneration of injured and compensatory sprouting of uninjured axons. Nogo-A is present in humans, making its neutralization a possible novel treatment option for paraplegic patients. In this study we examined the effects of an extensively used anti-Nogo-A antibody (mAb IN-1) on the regenerative capabilities of lesioned corticospinal tract (CST) axons in a primate, the Marmoset monkey. Unilateral thoracic lesions of the CST were performed in six adult Marmosets, followed by the application of mAb IN-1 into the cerebrospinal fluid circulation by a graft of hybridoma cells. A unilateral injection of biotin dextran amine into the motor cortex was performed to analyse sprouting and regeneration of the lesioned axons. In the control antibody-treated animal CST fibers stopped rostral to the lesion site and often showed retraction bulbs. In contrast, in four out of five mAb IN-1-treated animals fine labeled neurites had grown into, through and around the lesion site. Thus, this study provides first anatomical evidence that in primates, the neutralization of the myelin-associated inhibitor Nogo-A results in increased regenerative sprouting and growth of lesioned spinal cord axons.