METHODS AND COMPOSITIONS FOR TREATING MULTIPLE SCLEROSIS AND RELATED DISORDERS
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 . A complex comprising: a nanoparticle; a MHC protein and a multiple sclerosis-related antigen.
2 . The complex of claim 1 , wherein the nanoparticle has a diameter selected from the group of: from about 1 nm to about 100 nm in diameter; from about 1 nm to about 50 nm in diameter or from about 1 nm to about 20 nm or from about 5 nm to about 20 nm in diameter.
3 . The complex of claim 1 , wherein the ratio of the number of antigen-MHC complexes to nanoparticles is from about 10:1 to about 1000:1.
4 . The complex of claim 1 , wherein the antigen is an antigen derived from a protein selected from the group consisting of myelin basic protein, myelin associated glycoprotein, myelin oligodendrocyte protein, proteolipid protein, oligodendrocyte myelin oligoprotein, myelin associated oligodendrocyte basic protein, oligodendrocyte specific protein, heat shock proteins, oligodendrocyte specific proteins NOGO A, glycoprotein Po, peripheral myelin protein 22, and 2′3′-cyclic nucleotide 3′-phosphodiesterase and myelin oligodendrocyte glycoprotein (MOG) or an antigen corresponding to a peptide having at least 80% identity to a peptide comprising the sequence of SEQ ID NO: 1 or a polypeptide encoded by a polynucleotide that hybridizes under conditions of moderate to high stringency to a polynucleotide that encodes a sequence of SEQ ID NO: 1 or one having at least about 80% sequence identity to a sequence of SEQ ID NO: 1 or a complement of each thereof.
5 . The complex of claim 1 , wherein the nanoparticle is non-liposomal.
6 . The complex of claim 1 , wherein the antigen-MHC complex is covalently or non-covalently linked to the nanoparticle.
7 . The complex of claim 1 , wherein the antigen-MHC complex is covalently linked to the nanoparticle through a linker less than 5 kD in size.
8 . The complex of claim 1 , wherein the nanoparticle is bioabsorbable and/or biodegradable.
9 . The complex of claim 1 , wherein the MHC of the antigen-MHC-nanoparticle complex is a MHC class I or II.
10 . The complex of claim 1 , wherein the ratio of the number of antigen-MHC complexes to nanoparticles is from about 10:1 to about 1000:1.
11 . An isolated and purified polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or a polypeptide having at least about 80% sequence identity to SEQ ID NO: 1 or a polypeptide encoded by a polynucleotide that hybridizes under conditions of moderate to high stringency to a polynucleotide that encodes SEQ ID NO: 1 or one having at least about 80% sequence identity to SEQ ID NO: 1 or a complement thereof.
12 . An isolated and purified polynucleotide encoding the polypeptide of claim 11 , or an equivalent, or a polynucleotide that hybridizes under stringent conditions to the polynucleotide, its equivalent or its complement.
13 . A composition comprising a therapeutically effect amount of the complex of any one of claims 1 - 10 and a carrier.
14 . A composition comprising an effective amount of the polypeptide of claim 11 and a carrier.
15 . A composition comprising an effective amount of the polynucleotide of claim 12 and a carrier.
16 . A method for making, preparing or obtaining the complex of claim 1 , comprising coating antigen-MHC complexes onto a nanoparticle, wherein the antigen is a multiple sclerosis-related antigen.
17 . A method for expanding and/or developing populations of anti-pathogenic autoreactive T-cells in a subject with multiple sclerosis or a multiple sclerosis-related disorder, comprising administering to the subject an effective amount of an antigen-MHC-nanoparticle complex of any one of claims 1 - 10 .
18 . A method for treating multiple sclerosis or a multiple sclerosis related disorder in a subject in need thereof comprising administering to the subject an effective amount of an antigen-MHC-nanoparticle complex of any one of claims 1 - 10 .
19 . The method of claim 17 , wherein the multiple sclerosis-related disorder is selected from the group consisting of neuromyelitis optica (NMO), uveitis, and neuropathis pain.
20 . The method of claim 18 , wherein the multiple sclerosis-related disorder is selected from the group consisting of neuromyelitis optica (NMO), uveitis, and neuropathis pain.