Disclosed is an in vitro method for promoting survival of an oligodendrocyte, the method comprising contacting an oligodendrocyte with an effective amount of a composition comprising an Sp35 antagonist selected from the group consisting of: (i) a soluble Sp35 polypeptide that lacks an Sp35 immunoglobulin (Ig) domain (ii) an Sp35 antibody or antigen binding fragment thereof and (iii) a combination of two or more of the Sp35 antagonists, wherein said method inhibits the binding of an Sp35 polypeptide with an ErbB2 polypeptide or wherein said method increases ErbB2 phosphorylation. Also disclosed is the Use of an Sp35 antagonist selected from the group consisting of: (i) a soluble Sp35 polypeptide that lacks an Sp35 immunoglobulin (Ig) domain (ii) an Sp35 antibody or antigenbinding fragment thereof and (iii) a combination of two or more of the Sp35 antagonists, and an ErbB2 binding agent selected from the group consisting of: (i) a soluble ErbB2 polypeptide (ii) an ErbB2 antibody or antigen-binding fragment thereof (iii) an ErbB2 polynucleotide which encodes a soluble ErbB2 polypeptide and (iv) a combination of two or more of the ErbB2 binding agents, in the preparation of a medicament for treating a disease, disorder or injury associated with oligodendrocyte death, wherein said medicament is formulated to provide sequential administration or co-administration of the Sp35 antagonist and the ErbB2 binding agent.
