The invention provides methods of treating diseases, disorders or injuries involving demyelination and dysmyelination, including multiple sclerosis, by the administration of an Sp35 antagonist. Additional methods include methods for inhibiting the binding of the Sp35 polypeptide with the ErbB2 polypeptide and a method for increasing ErbB2 phosphorylation by contacting oligodendrocytes with an effective amount of a composition comprising an Sp35 antagonist of the invention. Further embodiments of the invention include methods of inhibiting the binding of the Sp35 polypeptide with the ErbB2, increasing ErbB2 phosphorylation and promoting oligodendrocyte differentiation comprising contacting oligodendrocyte or oligodendrcoyte progenitor cells with an ErbB2 binding agent.
