Methods for assessing the ability of a candidate drug to suppress MHC class I expression
First Claim
1. A method for assessing the therapeutic potential of a candidate drug for treating autoimmune diseases by assessing the ability of said candidate drug to suppress MHC Class I molecules, said method comprising,(a) treating mammalian cells with said drug;
- (b) obtaining protein extracts from said cells in step (a) and combining said protein extracts with a MHC Class I regulatory nucleic acid sequence to allow formation of complexes between at least one protein from said extract and said MHC class I regulatory nucleic acid sequence;
(c) detecting said complexes;
wherein a decrease or increase in quantity of said complexes indicates said drug'"'"'s potential in treating autoimmune diseases, said autoimmune diseases being selected from the group consisting of rheumatoid arthritis, psoriasis, juvenile diabetes, primary idiopathic myxedema, systemic lupus erythematosus, autoimmune asthma, myasthenia gravis, scleroderma, chronic hepatitis, Addison'"'"'s disease, hypogonadism, pernicious anemia, vitiligo, alopecia areata, Coeliac disease, autoimmune enteropathy syndrome, idiopathic thrombocytic purpura, acquired splenic atrophy, idiopathic diabetes insipidus, infertility due to antispermatazoan antibodies, sudden hearing loss, sensoneural hearing loss, Sjogren'"'"'s Syndrome, polymyositis, autoimmune demyelinating diseases, multiple sclerosis, transverse myelitis, ataxic sclerosis, pemphigus, progressive systemic sclerosis, dermatomyositis, polyarteritis nodosa, chronic hepatitis, hemolytic anemia, progressive systemic sclerosis, glomerular nephritis and idiopathic facial paralysis.
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Abstract
The present invention provides methods for treating autoimmune diseases in mammals and for preventing or treating transplantation rejection in a transplant recipient. The methods of treatment involve the use of drugs capable of suppressing expression of MHC Class I molecules. In particular the use of the drug methimazole to suppress expression of MHC Class I molecules in the treatment of autoimmune diseases and the prevention or treatment of rejection in a transplant recipient is disclosed. In addition in vivo and in vitro assays are provided for the assessment and development of drugs capable of suppressing MHC Class I molecules.
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Citations
17 Claims
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1. A method for assessing the therapeutic potential of a candidate drug for treating autoimmune diseases by assessing the ability of said candidate drug to suppress MHC Class I molecules, said method comprising,
(a) treating mammalian cells with said drug; -
(b) obtaining protein extracts from said cells in step (a) and combining said protein extracts with a MHC Class I regulatory nucleic acid sequence to allow formation of complexes between at least one protein from said extract and said MHC class I regulatory nucleic acid sequence; (c) detecting said complexes;
wherein a decrease or increase in quantity of said complexes indicates said drug'"'"'s potential in treating autoimmune diseases, said autoimmune diseases being selected from the group consisting of rheumatoid arthritis, psoriasis, juvenile diabetes, primary idiopathic myxedema, systemic lupus erythematosus, autoimmune asthma, myasthenia gravis, scleroderma, chronic hepatitis, Addison'"'"'s disease, hypogonadism, pernicious anemia, vitiligo, alopecia areata, Coeliac disease, autoimmune enteropathy syndrome, idiopathic thrombocytic purpura, acquired splenic atrophy, idiopathic diabetes insipidus, infertility due to antispermatazoan antibodies, sudden hearing loss, sensoneural hearing loss, Sjogren'"'"'s Syndrome, polymyositis, autoimmune demyelinating diseases, multiple sclerosis, transverse myelitis, ataxic sclerosis, pemphigus, progressive systemic sclerosis, dermatomyositis, polyarteritis nodosa, chronic hepatitis, hemolytic anemia, progressive systemic sclerosis, glomerular nephritis and idiopathic facial paralysis. - View Dependent Claims (2, 4, 8, 9, 10, 11, 12, 13, 14)
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3. A method for assessing the therapeutic potential of a candidate drug for treating transplantation rejection by assessing the ability of said candidate drug to suppress MHC Class I molecules, said method comprising,
(a) treating mammalian cells with said drug; -
(b) obtaining protein extracts from said cells in step (a) and combining said protein extracts with a MHC Class I regulatory nucleic acid sequence to allow formation of complexes between at least one protein from said extract and said MHC Class I regulatory nucleic sequence; (c) detecting said complexes;
wherein a decrease or increase in the quantity of said complexes indicates said drug'"'"'s potential in treating transplantation rejection.
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5. A method for assessing the therapeutic potential of a candidate drug for treating autoimmune diseases by assessing the ability of a candidate drug to suppress MHC Class I molecules, said method comprising:
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(a) introducing a reporter gene operably linked to a MHC Class I regulatory sequence into a population of mammalian cells; (b) treating said cells with said drug; and (c) measuring activity of said reporter gene operably linked to said MHC Class I regulatory sequence, whereby decreased activity indicates said drug'"'"'s potential in treating autoimmune diseases, said autoimmune diseases being selected from the group consisting of rheumatoid arthritis, psoriasis, juvenile diabetes, primary idiopathic myxedema, systemic lupus erythematosus, autoimmune asthma, myasthenia gravis, scleroderma, chronic hepatitis, Addison'"'"'s disease, hypogonadism, pernicious anemia, vitiligo, alopecia areata, Coeliac disease, autoimmune enteropathy syndrome, idiopathic thrombocytic purpura, acquired splenic atrophy, idiopathic diabetes insipidus, infertility due to antispermatazoan antibodies, sudden hearing loss, sensoneural hearing loss, Sjogren'"'"'s Syndrome, polymyositis, autoimmune demyelinating diseases, multiple sclerosis, transverse myelitis, ataxic sclerosis, pemphigus, progressive systemic sclerosis, dermatomyositis, polyarteritis nodosa, chronic hepatitis, hemolytic anemia, progressive systemic sclerosis, glomerular nephritis and idiopathic facial paralysis. - View Dependent Claims (7, 15, 16, 17)
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6. A method for assessing the therapeutic potential of a candidate drug for treating transplantation rejection by assessing the ability of a candidate drug to suppress MHC Class I molecules, said method comprising:
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(a) introducing a reporter gene operably linked to a MHC Class I regulatory sequence into a population of mammalian cells; (b) treating said cells with said drug; and (c) measuring activity of said reporter gene operably linked to said MHC Class I regulatory sequence, whereby decreased activity indicates said drug'"'"'s potential in treating transplantation rejection.
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Specification