53 results about "OI - Osteogenesis imperfecta" patented technology

This invention relates to pyrimidine compounds of formula (I), formula (I′), and formula (I″):and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, R5, U, V, W, X, Y, Z, and n are defined herein. This invention also relates to compositions comprising these compounds and methods for using them. The compounds and compositions of this invention are useful to treat or prevent disorders associated with excessive bone loss, including, without limitation periodontal disease, non-malignant bone disorders (such as osteoporosis, Pagers-disease of bone, osteogenesis imperfecta, fibrous dysplasia, and primary hyperparathyroidism) estrogen deficiency, inflammatory bone loss, bone malignancy, arthritis, osteopetrosis, and certain cancer-related disorders (such as hypercalcemia of malignancy (HCM), osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer and other metastatic cancers).

This invention relates to pyrimidine compounds of formula (I), formula (I′), and formula (I″): and pharmaceutically acceptable salts, solvates, clathrates, and prodrugs thereof, wherein R1, R2, R3, R4, R5, U, V, W, X, Y, Z, and n are defined herein. This invention also relates to compositions comprising these compounds and methods for using them. The compounds and compositions of this invention are useful to treat or prevent disorders associated with excessive bone loss, including, without limitation periodontal disease, non-malignant bone disorders (such as osteoporosis, Pagers-disease of bone, osteogenesis imperfecta, fibrous dysplasia, and primary hyperparathyroidism) estrogen deficiency, inflammatory bone loss, bone malignancy, arthritis, osteopetrosis, and certain cancer-related disorders (such as hypercalcemia of malignancy (HCM), osteolytic bone lesions of multiple myeloma and osteolytic bone metastases of breast cancer and other metastatic cancers).

The present invention relates to a method to enhance the activity of Runx2, a major target protein of Bone Mophogenetic Protein (BMP), by Runx2 acetylation, more precisely, a method to activate BMP-mediated bone formation pathway by protecting Runx2 from ubiquitination, indicating that Runx2 is protected from degradation by the increase of Runx2 acetylation making the protein more stable. The method to enhance Runx2 activity of the present invention can be utilized for the prevention and the treatment of bone disease such as osteoporosis, osteogenesis imperfecta, periodontal disease and fracture, by inducing bone formation by inhibiting Runx2 degradation.

The invention relates to a mutation site of an XI-type osteogenesis imperfecta pathogenic gene FKBP10 and application of the mutation site. A whole genome resequencing technology is combined with comprehensive technologies of digital PCR, Sanger sequencing and the like; whole genome resequencing is carried out for clinic suspected osteogenesis imperfect patients; the condition that copy number variation exists between an exon 2 to an exon 4 of the FKBP10 gene and meanwhile, a heterozygous shear site mutation that c.918-3C is greater than G is discovered by combining with bioinformatics. Copy number variation and heterozygous shear mutation between the exon 2 to the exon 4 of the FKBP10 gene are further validated through digital PCR and a traditional PCB-based Sanger sequencing technology separately. Through discovery of the copy number variation and the heterozygous shear mutation, basis and reference are provided for discussing pathogenesis of XI-type osteogenesis imperfect and enriching and developing a diagnosis method for clinical diagnosis and treatment, and a basic basis is provided for early pathogenic gene screening and treatment.

The invention relates to a method for co-expression of Runx2 and Osterix in mesenchymal stem cells or other non-osteoblasts by a special mode that the expression level of Runx2 is less than the expression level of Osterix, thus speeding up the induction of osteoblast differentiation. The invention provides a pharmaceutical composition for prevention or treatment of osteoblast differentiation related diseases. The pharmaceutical composition contains Runx2 protein and Osterix protein, wherein the Runx2 protein content is smaller than the Osterix protein content. The invention also provides application of the Runx2 protein and the Osterix protein in preparation of the pharmaceutical composition for prevention or treatment of osteoblast differentiation related diseases, and in the pharmaceutical composition, the content of the Runx2 protein is less than that of the Osterix protein. The pharmaceutical composition and the special co-expression mode of Runx2 and Osterix provided in the invention can be used for treatment of osteoporosis, osteogenesis imperfecta, periodontal diseases, fractures and other bone diseases, and also can be used for research, development and production of tissue-engineered bones. The invention also provides a method for screening drugs preventing and treating bone diseases.

The invention provides methods for treating or preventing bone degenerative disorders. The disorders treated or prevented include, for example, osteopenia, osteomalacia, osteoporosis, osteomyeloma, osteodystrophy, Paget's disease, osteogenesis imperfecta, and bone degenerative disorders associated with chronic renal disease, hyperparathyroidism, and long-term use of corticosteroids. The disclosed therapeutic methods include administering to a mammal an inhibitor of GDF-9 or BMP-15 in an amount effective to: (1 ) treat or prevent a bone degenerative disorder; (2) slow bone deterioration; (3) restore lost bone; (4) stimulate new bone formation; and / or (5) maintain bone mass and / or bone quality. The invention also provides methods for administering a GDF-9 agonist or a BMP-15 agonist to treat a bone disorder characterized by increased bone density or mass.

The present invention relates to compounds of Formula (I),methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury / loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

The present invention relates to compounds of Formula (I),methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury / loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

Disclosed are methods for treating a patient suffering from osteogenesis imperfecta comprising administering to the patient a therapeutically effective amount of an anti-sclerostin antibody. Methods for increasing bone formation and reducing bone resorption in an osteogenesis imperfecta patient by administering to the patient a therapeutically effective amount of an anti-sclerostin antibody are also disclosed. Further disclosed are compositions for increasing bone formation and reducing bone resorption in an osteogenesis imperfecta patient. The compositions comprise a therapeutically effective amount of an anti-sclerostin antibody. The invention also provides an anti-sclerostin antibody for use in the treatment of osteogenesis imperfecta.

The invention provides methods for treating or preventing bone degenerative disorders. The disorders treated or prevented include, for example, osteopenia, osteomalacia, osteoporosis, osteomyeloma, osteodystrophy, Paget's disease, osteogenesis imperfecta, and bone degenerative disorders associated with chronic renal disease, hyperparathyroidism, and long-term use of corticosteroids. The disclosed therapeutic methods include administering to a mammal an inhibitor of GDF-9 or BMP-15 in an amount effective to: (1) treat or prevent a bone degenerative disorder; (2) slow bone deterioration; (3) restore lost bone; (4) stimulate new bone formation; and / or (5) maintain bone mass and / or bone quality. The invention also provides methods for administering a GDF-9 agonist or a BMP-15 agonist to treat a bone disorder characterized by increased bone density or mass.

The invention provides primers and a kit for amplification and mutation site detection of human COL1A1 and / or COL1A2 genes, and belongs to the technical field of gene detection. The kit for detectingthe DNA mutation of the human COL1A1 and / or COL1A2 genes comprises a sequencing primer group for detecting the mutation of the 1st to 52nd exons of the COL1A1 and COL1A2 genes. By adopting the specific primer group for mutation detection of the first exon to the 52nd exon of the COL1A1 gene and the COL1A2 gene, the accuracy and specificity of a measurement result are ensured; gene detection is carried out on hereditary diseases such as osteogenesis imperfectaI-IV type, Ehlers-Danlos syndrome, Caffey's disease, osteogenesis imperfectaand Ehlers-Danlos syndrome complications and the like causedby COL1A1 and COL1A2 gene mutation. The kit can be used for gene detection of complex diseases associated with COL1A1 and COL1A2 gene mutation.

The invention discloses a traditional Chinese medicine composition for treating osteogenesis imperfecta, which is prepared from the following raw material in certain proportion: astragalus membranaceus, angelica sinensis, rhizoma chuanxiong, parched white peony root, radix codonopsis, roasted rhizoma atractylodis macrocephalae, poria cocos, fructus lycii, semen cuscutae, fructus psoraleae, cassia twig, herba taxilli, dipsacus asperoids, flatstem milkvetch seed, prepared rehmannia root, cortex eucommiae, radix moridae officinalls, artemisia anomala, eclipta, rhizoma cyperi and radix liquiritiae. The traditional Chinese medicine composition has the effects of nourishing liver and kidney, replenishing blood, nourishing liver, tonifying middle-Jiao and Qi, promoting blood circulation to arrest pain, invigorating kidney and spleen, promoting bone reunion, and strengthening tendons and bones, and can effectively treat osteogenesis imperfecta.

The present invention provides methods for treating and improving the symptoms of osteogenesis imperfecta (OI) in a subject by administering to the subject a therapeutically effective amount of a binding agent that binds to transforming growth factor beta (TGFbeta).

The invention provides methods for treating or preventing bone degenerative disorders. The disorders treated or prevented include, for example, osteopenia, osteomalacia, osteoporosis, osteomyeloma, osteodystrophy, Paget's disease, osteogenesis imperfecta, and bone degenerative disorders associated with chronic renal disease, hyperparathyroidism, and long-term use of corticosteroids. The disclosed therapeutic methods include administering to a mammal an inhibitor of GDF-9 or BMP-15 in an amount effective to: (1) treat or prevent a bone degenerative disorder; (2) slow bone deterioration; (3) restore lost bone; (4) stimulate new bone formation; and / or (5) maintain bone mass and / or bone quality. The invention also provides methods for administering a GDF-9 agonist or a BMP-15 agonist to treat a bone disorder characterized by increased bone density or mass.

The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment non-soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of non-soft tissue (e.g. bone). Also provided are methods of isolating muscle-derived progenitor cells, and methods of genetically modifying the cells for gene transfer therapy. The invention further provides methods of using compositions comprising muscle-derived progenitor cells for the augmentation and bulking of mammalian, including human, bone tissues in the treatment of various functional conditions, including osteoporosis, Paget's Disease, osteogenesis imperfecta, bone fracture, osteomalacia, decrease in bone trabecular strength, decrease in bone cortical strength and decrease in bone density with old age.

The present invention provides muscle-derived progenitor cells that show long-term survival following transplantation into body tissues and which can augment non-soft tissue following introduction (e.g. via injection, transplantation, or implantation) into a site of non-soft tissue (e.g. bone) when combined with a biocompatible matrix, preferably SIS. The invention further provides methods of using compositions comprising muscle-derived progenitor cells with a biocompatible matrix for the augmentation and bulking of mammalian, including human, bone tissues in the treatment of various functional conditions, including osteoporosis, Paget's Disease, osteogenesis imperfecta, bone fracture, osteomalacia, decrease in bone trabecular strength, decrease in bone cortical strength and decrease in bone density with old age.