While we do think that overexpressing Sema3F in MS lesions as early as possible (young patients with relapsing–remitting disease) would be the most optimal in stimulating remyelination to prevent neurodegeneration, conserved OPC responses to Sema3F in middle‐aged mice suggest that such therapy may also be beneficial in early stages of progressive disease (most frequently occurring in middle‐age individuals) to limit further axonal loss by enhancing remyelination of expanding lesions. Here, SEMA3F is linked to myeloid sarcoma.