Methods and compositions for treating multiple sclerosis and related disorders

Abstract

This disclosure provides therapeutic compositions and methods for treating multiple sclerosis or a multiple sclerosis-related disorder in a subject in need thereof comprising administering an effective amount of an antigen-MHC-nanoparticle complex to the subject, wherein the antigen is a multiple sclerosis-related antigen.

1 .- 31 . (canceled) 
     
     
         32 . A nanoparticle complex comprising:
 a nanoparticle core and multiple sclerosis-related antigen-MHC (pMHC) complexes operatively coupled to the nanoparticle core,   wherein the nanoparticle core has a diameter from about 1 nm to about 100 nm;   wherein the pMHC density on the nanoparticle core comprises from about 0.005 pMHC/100 nm 2  to about 25 pMHC/100 nm 2 ; and   wherein the multiple sclerosis-related antigen of the pMHC complex comprises the polypeptide sequence that is SEQ ID NO: (pMOG 38-49 ).   
     
     
         33 . The nanoparticle complex of 32, wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm. 
     
     
         34 . The nanoparticle complex of  claim 33 , wherein the nanoparticle core has a diameter from about 1 nm to about 20 nm. 
     
     
         35 . The nanoparticle complex of  claim 34 , wherein the nanoparticle core has a diameter from about 5 nm to about 20 nm. 
     
     
         36 . The nanoparticle complex of  claim 32 , wherein the nanoparticle core has a biodegradable layer on the outer surface of the nanoparticle core and the pMHC complexes are operatively coupled to the nanoparticle core or the biodegradable layer on the nanoparticle core. 
     
     
         37 . The nanoparticle complex of  claim 36 , wherein the biodegradable layer comprises one or more of dextran, mannitol, or poly(ethylene glycol). 
     
     
         38 . The nanoparticle complex of  claim 36 , wherein the nanoparticle core has a diameter from about 1 nm to about 50 nm. 
     
     
         39 . The nanoparticle complex of  claim 38 , wherein the nanoparticle core has a diameter from about 1 nm to about 20 nm. 
     
     
         40 . The nanoparticle complex of  claim 39 , wherein the nanoparticle core has a diameter from about 5 nm to about 20 nm. 
     
     
         41 . The nanoparticle complex of  claim 32 , wherein the pMHC complexes are covalently or non-covalently linked to the nanoparticle core or the biodegradable layer. 
     
     
         42 . The nanoparticle complex of  claim 32 , wherein the pMHC complexes are covalently linked to the nanoparticle core or the biodegradable layer through a linker less than 5 kD in size. 
     
     
         43 . The nanoparticle complex of  claim 42 , wherein the linker comprises polyethylene glycol. 
     
     
         44 . The nanoparticle complex of  claim 32 , wherein the nanoparticle core is bioabsorbable and/or biodegradable. 
     
     
         45 . The nanoparticle complex of  claim 32 , wherein the MHC of the pMHC complexes is a MHC class I or II protein. 
     
     
         46 . The nanoparticle complex of  claim 45 , wherein the MHC class I protein comprises all or part of a HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G or CD-1 protein. 
     
     
         47 . The nanoparticle complex of  claim 45 , wherein the MHC class II protein comprises all or part of a HLA-DR, HLA-DQ, or HLA-DP protein. 
     
     
         48 . The nanoparticle complex of  claim 32 , wherein the ratio of the number of pMHC complexes to the nanoparticle core is from about 10:1 to about 500:1. 
     
     
         49 . A composition comprising a therapeutically effect amount of the complex of  claim 32  and a carrier.