Endogenous Sp35 is a negative regulator of neuronal survival, axon regeneration, oligodendritis differentiation and myelination. Molecules that block the function of endogenous Sp35, such as antibodies to Sp35, can be used as drugs to treat neuronal dysfunction and oligodendrites. The present invention provides antibodies specific for Sp35 and methods for using these antibodies as antagonists of endogenous Sp35 function. The invention further provides for specific hybridoma and monoclonal antibodies, nucleic acids isolated from phage libraries, which encode these antibodies, and vectors and host cells, including these antibodies. In addition, the invention provides methods that stimulate the survival of oligodendrites and myelination of vertebrates, including the introduction of an effective amount of an anti-Sp35 antibody to vertebrates in need of treatment.
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