In the recent years, several pro-myelinating agents have been identified (Melchor et al., 2019). Among them, clemastine fumarate an anti-muscarinic compound, has been recognized as a potent agent promoting anatomical and clinical recovery in rodents (Mei et al., 2014, Cordano et al., 2023) and primary efficacy in clinic (Green et al., 2017). Although the clinical trial REBUILD showed reduced visual evoked latencies (VEP) in RRMS patients treated with clemastine, the impact of clemastine on myelin repair in the absence of post-mortem validation, remained elusive. We took advantage of a recently developed model of chronic demyelination of the adult macaque optic nerve, associated with axon degeneration and visual deficits (Sarrazin et al., 2022), to investigate whether clemastine fumarate can activate optic nerve repair and thereby, prevent axonal degeneration and visual deficits in non-human primates. We used VEP, OCT and ERG as non-invasive means to follow up the process of optic nerve de/remyelination and correlated these findings with post-mortem analysis to establish the safety and efficacy of clemastine therapy in an animal model close to man. Our findings highlight that clemastine can activate myelin repair in chronic lesions of the macaque optic nerve and is able to some extend to prevent lesion-induced degeneration of the retina both at the anatomical and functional levels. Supported this by the International Associated Laboratory “Neuro-Bridge” and the NIH/NINDS SRO1NS105741-02