As current treatments for
multiple sclerosis (MS) remain chemotherapeutic ones directed toward symptoms, the development of a curative treatment is urgently required. Herein, we show an autoreactive immune cell-targetable approach using
autoantigen-modified
liposomes for the curative treatment of MS. In these experiments,
experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic
myelin oligodendrocyte glycoprotein (MOG)
peptide was used as a model of primary progressive MS, and MOG-modified
liposomes encapsulating
doxorubicin (MOG-LipDOX) were used as a therapeutic drug. The results showed that the progression of
encephalomyelitis symptoms was significantly suppressed by MOG-LipDOX injection, whereas the other samples failed to show any effect. Additionally, invasion of inflammatory immune cells into the spinal cord and
demyelination of neurons were clearly suppressed in the MOG-LipDOX-treated mice. FACS analysis revealed that the number of both MOG-recognizable CD4+ T cells in the spleen was obviously decreased after MOG-LipDOX treatment. Furthermore, the number of effector Th17 cells in the spleen was significantly decreased and that of regulatory Treg cells was concomitantly increased. Finally, we demonstrated that
myelin proteolipid protein (PLP)-modified
liposomes encapsulating DOX (PLP-LipDOX) also showed the
therapeutic effect on relapsing-remitting EAE. These findings indicate that
autoantigen-modified liposomal drug produced a highly
therapeutic effect on EAE by delivering the encapsulated drug
to autoantigen-recognizable CD4+ T cells and thus suppressing autoreactive immune responses. The present study suggests that the use of these
autoantigen-modified
liposomes promises to be a suitable therapeutic approach for the cure of MS.