Osteoporosis treatment

Abstract

There is disclosed a process of treating or alleviating the symptoms of pathological conditions in which bone density is decreased, which comprises inhibiting, in a mammalian patient suffering from such a condition, the formation in vivo of a tertiary complex of IL-11, its cell surface membrane receptor and the cell surface glycoprotein gp130. Examples of such substances are recombinant soluble IL-11 receptor mutants modified, as compared with native IL-11 receptor, at their gp130 binding site, and peptides which can interact with IL-11. The process of the invention not only inhibits bone resorption and hence bone loss, but also increases the process of bone formation to increase bone density.

What is claimed is:  
     
         1 . A process of increasing bone density in a mammalian patient suffering from a pathological condition in which bone density is decreased which comprises inhibiting the formation of a tertiary complex of IL-11, IL-11R and gp130.  
     
     
         2 . The process of  claim 1  which comprises administering to the patient an effective amount of a substance which inhibits, in vivo, the formation of a tertiary complex of IL-11, IL-11R, and gp130.  
     
     
         3 . The process of  claim 2  wherein the pathological condition is postmenopausal bone loss.  
     
     
         4 . The process of  claim 2  wherein the substance is a mutant IL-11R.  
     
     
         5 . The process of  claim 4  wherein the substance is a mutant IL-11R with at least-one mutation in its gp130 binding region.  
     
     
         6 . The process of  claim 5  wherein the substance is a mutant IL-11R having at least one of the following mutations: D282→G282, A283→D283, G286→D286, H289→Y289, and V291→L291.  
     
     
         7 . The process of  claim 6  wherein the substance is a mutant IL-11R having the mutation H289→Y289.  
     
     
         8 . The process of  claim 4 , wherein the substance is a soluble mutant IL-11R.  
     
     
         9 . The process of  claim 8  wherein the mutant IL-11R is a human IL-11R.  
     
     
         10 . The process of  claim 2  wherein the substance is an anti IL-11 antibody.  
     
     
         11 . The process of  claim 2  wherein the substance is an IL-11 binding peptide.  
     
     
         12 . The process of  claim 11  wherein the substance is an IL-11 binding peptide having an amino acid sequence which specifically binds IL-11 in the region normally bound by IL-11R.  
     
     
         13 . The process of  claim 12  wherein the substance is a peptide comprising the sequence Arg Arg Leu Arg Ala Ser Trp.  
     
     
         14 . The process of  claim 2  wherein the substance is a small molecule.  
     
     
         15 . The process of  claim 2  wherein the substance is an IL-11 antagonist.  
     
     
         16 . The process of  claim 2  wherein the substance is an IL-11R binding peptide.  
     
     
         17 . The process of  claim 2  wherein the substance is an anti IL-11R antibody which inhibits interactions between IL-11 and the IL-11R.  
     
     
         18 . The process of  claim 2  wherein the substance is an anti IL-11R antibody which inhibits interactions between IL-11R and gp130.  
     
     
         19 . The process of  claim 2  wherein the substance is an effective amount of transcribable genetic material which causes inhibition of the formation of the tertiary complex of IL-11, IL-11R, and gp130.  
     
     
         20 . The process of  claim 19  wherein the transcribable genetic material encodes an RNA sequence capable of inhibiting the translation of a component necessary to the formation of the IL-11/IL-11R/gp130 tertiary complex.  
     
     
         21 . The process of  claim 20  wherein the transcribable genetic material comprises DNA encoding an RNA sequence complementary to IL-11 mRNA.  
     
     
         22 . The process of  claim 20  wherein the transcribable genetic material comprises DNA encoding an RNA sequence complementary to IL-11R mRNA.  
     
     
         23 . The process of  claim 20  wherein the transcribable genetic material comprises DNA encoding an RNA sequence complementary to gp130 mRNA.  
     
     
         24 . The process of  claim 19  wherein the transcribable genetic material comprises DNA encoding an amino acid sequence capable of inhibiting the formation of the IL-11/IL-11R/gp130 tertiary complex.  
     
     
         25 . The process of  claim 24  wherein the transcribable genetic material encodes an IL-11R mutated to inhibit binding to gp130.  
     
     
         26 . The process of  claim 24  wherein the transcribable genetic material encodes an IL-11 binding peptide.  
     
     
         27 . The process of  claim 19 , wherein the level of transcription of the transcribable genetic material is dependant on the concentration of an inducing compound.  
     
     
         28 . The process of  claim 1 , in which the patient is a human.  
     
     
         29 . A composition of matter comprising a mutant IL-11R.  
     
     
         30 . The composition of  claim 29  in which the mutant IL-11R has at least one of the following mutations: D282→G282, A283→D283, G286→D286, H289→Y289, and V291→L291.  
     
     
         31 . The composition of  claim 30  in which the mutant IL-11R has the H289→Y289 mutation.  
     
     
         32 . The composition of  claim 29 , wherein the mutant IL-11R is soluble.  
     
     
         33 . The composition of  claim 29 , wherein the mutant IL-11R is a human IL-11R.  
     
     
         34 . A composition of matter comprising an IL-11 binding peptide.  
     
     
         35 . The composition of  claim 34  wherein the IL-11 binding peptide comprises the sequence Arg Arg Leu Arg Ala Ser Trp.  
     
     
         36 . The composition of  claim 34  wherein the IL-11 binding peptide comprises the sequence Arg Arg Leu His Ala Ser Trp.  
     
     
         37 . The composition of  claim 34  wherein the IL-11 binding peptide comprises the sequence Arg Arg Leu X Ala Ser Trp, and X is a basic amino acid.  
     
     
         38 . The composition of  claim 34  wherein the IL-11 binding peptide comprises the sequence Ser Ile Leu Arg Pro Asp Pro Pro Gln Gly Leu Arg Val Glu Ser Val Pro Gly Tyr Pro.  
     
     
         39 . The composition of  claim 34  wherein the IL-11 binding peptide comprises the sequence Ser Ile Leu Arg Pro Asp Pro Pro Gln Gly Leu Arg Val Glu Ser Val Pro Ser Tyr Pro.  
     
     
         40 . Use of the peptide of  claim 34  in reducing the formation of a tertiary complex of IL-11, IL-11R and gp130.  
     
     
         41 . Use of the peptide of  claim 34  in the purification of IL-11.  
     
     
         42 . Use of the peptide of  claim 34  in the depletion of IL-11 from a solution.  
     
     
         43 . A composition of matter for the selective binding of IL-11 comprising the peptide of  claim 34  suitably immobilized on an appropriate substrate.  
     
     
         44 . A composition of matter comprising an IL-11R binding peptide.  
     
     
         45 . Use of an antibody which specifically binds the IL-11R and blocks interactions between IL-11 and IL-11R in the preparation of a medicament for use in increasing bone density in a mammalian patient.  
     
     
         46 . Use of an antibody which specifically binds the IL-11R and blocks interactions between gp130 and IL-11R in the preparation of a medicament for use in increasing bone density in a mammalian patient.  
     
     
         47 . The use of the TRAP assay in identifying IL-11 antagonists.  
     
     
         48 . The use of the bone marrow formation assay in identifying IL-11 antagonists.  
     
     
         49 . A process of increasing bone formation while decreasing bone resorption in a mammalian patient, which comprises inhibiting the formation of a tertiary complex of IL-11, IL-11R and gp130.