1183 results about "Bone disease" patented technology

The present invention provides antibodies and immunologically functional fragments thereof that specifically bind Dkk-1 polypeptides. The subject antibodies and fragments bind with high affinity to a conformational epitope located in the carboxy region of the Dkk-1 protein. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases including bone disorders, inflammatory diseases, neurological diseases, ocular diseases, renal diseases, pulmonary diseases and skin diseases are also disclosed.

Provided herein are methods for diagnosing and treating multiple myeloma based on statistical analysis of and subsequent increasing / inhibiting expression of subgroups of plasma cells and B cell genes. Also provided are methods for a developmental stage-based classification for multiple myeloma using hierarchical clustering analysis of plasma cell and B cell nucleic acids and for discriminating among normal, hyperplastic and malignant using gene expression array data and statistical analysis thereof. In addition methods for determining the risk of developing bone disease in a test individual by examining expression levels of a WNT signaling antagonist, such as DKK1, are provided. A kit comprising anti-DKK1 antibodies and detection reagents for measuring DKK1 protein levels also is provided.

Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-alpha converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-alpha from membrane bound TNF-alpha precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection having the formulawherein R2 and R3 form a heterocyclic ring and A is S, S(O), or S(O)2, and R1 and R4 are defined herein.

Disclosed are biomedical scaffolds that may be used, for example, for treatment of bone diseases and bone repair. Methods of preparing such scaffolds are also disclosed. These scaffolds permit nutrient and ion flow such that bone regeneration in the area surrounding the scaffold is promoted. Also disclosed are kits that include the scaffolds set forth herein.

The present invention is directed to isolated polypeptides and antibodies suitable for producing therapeutic preparations, methods, and kits relating to bone deposition. One objective of the present invention is to provide compositions that improve bone deposition. Yet another objective of the present invention is to provide methods and compositions to be utilized in diagnosing bone dysregulation. The therapeutic compositions and methods of the present invention are related to the regulation of Wise, Sost, and closely related sequences. In particular, the nucleic acid sequences and polypeptides include Wise and Sost as well as a family of molecules that express a cysteine knot polypeptide.

Compositions containing strontium fortified calcium nanoparticles and / or microparticles, and methods of making and using thereof are described herein. The strontium fortified calcium compounds contain calcium ions, calcium atoms, strontium ions, strontium atoms, and combinations thereof and one or more anions. Exemplary anions include, but are not limited to, citrate, phosphate, carbonate, and combinations thereof. The particles can be formulated for enteral or parenteral administration by incorporating the particles into a pharmaceutically carrier. The compositions can further contain one or more active agents useful for bone diseases or disorders, such as vitamin D, growth factors, and combinations thereof. The compositions can be used to treat or prevent one or more bone diseases or disorders of the bone, such as osteoporosis. Alternatively, the particles can be coated onto a substrate, such as the surface of an implant. The coatings can be used to improved biocompatibility of the implant, prevent loosening of the implant, reducing leaching of metal ions from metallic implants, and reduce corrosion. The coatings can be applied to the substrate using a variety of techniques well known in the art. In one embodiment, the coating is applied using electrophoretic deposition. The use of nano- and / or microparticles that provide high surface area helps to improve interfacial strength between the coating and the implant, which allows for the use of lower sintering temperatures. Lowering sintering temperatures minimizes or prevents thermal decomposition of the coating material and / or degradation of the implant material.

The disclosed embodiments provide a method for acquiring MR data at resolutions down to tens of microns for application in in vivo diagnosis and monitoring of pathology for which changes in fine tissue textures can be used as markers of disease onset and progression. Bone diseases, tumors, neurologic diseases, and diseases involving fibrotic growth and / or destruction are all target pathologies. Further the technique can be used in any biologic or physical system for which very high-resolution characterization of fine scale morphology is needed. The method provides rapid acquisition of signal at selected values in k-space, with multiple successive acquisitions at individual k-values taken on a time scale on the order of microseconds, within a defined tissue volume, and subsequent combination of the multiple measurements in such a way as to maximize SNR. The reduced acquisition volume, and acquisition of only signal values at select places in k-space, along selected directions, enables much higher in vivo resolution than is obtainable with current MRI techniques.

Disclosed are pharmaceutical compositions that comprise gallium complexes of 3-hydroxy-4-pyrones. These compositions provide enhanced gallium bioavailability particularly when orally administered as compared to the gallium bioavailability achieved by use of pharmaceutical compositions containing gallium salts. Compositions included in this invention are useful in providing gallium to humans and other mammals for a wide variety of medical and veterinary applications, including the treatment, prevention, or diagnosis of hypercalcemia, certain cancers, certain disorders of calcium homeostasis, and certain bone diseases including osteoporosis, osteopenia, and Paget's disease.

The present invention provides methods and kits for treating hyperparathyroidism, bone disease and / or hypercalcemic disorders. In particular, methods for lowering serum PTH and serum calcium using polycationic calcium modulator peptides are provided. The calcium modulator peptides can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

The present invention discloses agents and methods for inducing osteoblastic cellular differentiation, as well as the use of such agents and method to treat patients to maintain bone mass, enhance bone formation and / or bone repair. Exemplary agents include oxysterols, alone or in combination with particular oxysterols, or other agents known to assist in bone formation. The invention further includes medicaments including oxysterols for the treatment of bone disorders, local injections of oxysterols or cells (206) and implants (202) having agents or cells (203) to facilitate bone repair.

Compositions and methods for the treatment of bone diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2), acts to stimulate bone formation independently of Wnt proteins which may be inhibited and / or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3 / FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

Compounds that inhibit the activity of NF-κB or inhibit the activity of the proteasome or both promote bone formation and hair growth and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyrdidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation; they also stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

The invention relates to an exosome carrier of a targeted bone, a CRISPR / Cas9 gene editing system and application. The exosome carrier comprises a targeted peptide of any one of a targeted bone forming surface, a bone absorbing surface and an endothelial cell. The exosome carrier can be fused with (AspSerSer)6, (Asp)8 and a CREDVW oligopeptide respectively by transforming an exosome surface membrane protein lamp2b, so that an exosome can be fused with the targeted bone forming surface, the bone absorbing surface and the endothelial cell. Therefore, the bone targeting exosome is developed as the carrier, a CRISPR / Cas9 system serves as a gene editing and controlling tool, and the two parts are combined to play the important significance on the treatment of various bone diseases.

Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and / or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

The invention discloses a kit, an application thereof in detection on hereditary bone disease genes, and also a method and an apparatus for detection on the hereditary bone disease genes. The kit includes a probe which is fixed on a solid-phase substrate or is free in a solution. The probe can specially recognize exon regions of 722 or 363 genes, for example, the exon regions of the following nine genes: PHEX, ENPP1, FGF23, CLCN5, SLC34A3, DMP1, VDR, CYP2R1 and CYP27B1. The kit, and as well as the method and the apparatus for detection on the hereditary bone disease genes are used for one-time acquiring and / or detecting related genes of the hereditary bone disease and mutation status thereof.

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 subjects of this invention are pharmaceutical compositions that comprise gallium complexes of 3-hydroxy-4-pyrones. The compositions have been developed to provide pharmaceutically acceptable gallium bioavailability together with low toxicity, particularly for oral administration. Compositions included in this invention should be useful in providing gallium to humans and other animals for a wide variety of medical and veterinary applications, including the treatment, prevention, or diagnosis of certain bone diseases, certain cancers, and certain disorders of calcium homeostasis.

The present invention relates to novel compounds of formula (I)that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and / or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

A method for detecting bone and bone disease using MRI images includes: detecting and segmenting bone borders using dark bone border intensity information from an MRI image; and detecting bone disease within a segmented image region.

The present invention provides an efficient gene delivery system using Adeno-Associated Viral (AAV) vector in gene therapy. Furthermore, the invention provides a combined AAV and Adenovirus (Adv) cocktail gene delivery system which is even more efficient in in vivo gene delivery and expression without eliciting any significant immune responses in an immunocompetent subject. In particular, the invention provides a therapeutic agent and methods for preventing, treating, managing, or ameliorating various diseases and disorders including, but not limited to, bone diseases, by delivering Bone Morphogenetic Protein 2 (BMP-2) for new bone formation via gene therapy using said system. The invention provides a nucleic acid molecule comprising an AVV vector and a promoter operably linked to a sequence encoding BMP-2; and a nucleic acid molecule comprising an Adv vector and a promoter operably linked to a sequence encoding BMP-2, as well as vectors and host cells comprising said nucleic acid molecules, respectively.

Methods for identifying subjects having, or at risk for developing, osteoarthritis or other cartilage degenerative conditions by measuring levels of expression of F-spondin are provided. Assays, kits and methods for determining and assaying the presence of F-spondin in individual patients are disclosed. Oligonucleotide probes and primers for use in the assays, kits and methods are described. Assays and methods are disclosed for identifying candidate compounds that modulate F-spondin levels of expression and / or function or for determining and evaluating an individual's response to drugs and therapeutic agents, are provided. The invention further relates to the modulation of F-spondin, particularly the inhibition of F-spondin, for increasing or stimulating bone formation and / or growth and mediating the alleviation of bone disease, disorders or conditions. The use of F-spondin, an active fragment thereof, or a modulator thereof for enhancing cartilage repair or preventing or treating cartilage degeneration, degenerative diseases or arthritic conditions is also provided.

A novel polypeptide, osteoprotegerin binding protein, involved in osteolcast maturation has been identified based upon its affinity for osteoprotegerin. Nucleic acid sequences encoding the polypeptide, or a fragment, analog or derivative thereof, vectors and host cells for production, methods of preparing osteoprotegerin binding protein, and binding assays are also described. Compositions and methods for the treatment of bone diseases such as osteoporosis, bone loss due to arthritis or metastasis, hypercalcemia, and Paget's disease are also provided.

The present invention pertains to cannabinoid (CB) receptor inverse agonists and neutral antagonists, and especially CB1 and CB2 inverse agonists and neutral antagonists; such as, for example, certain pyrazole compounds; their use in the inhibition of osteoclasts (for example, the inhibition of the survival, formation, and / or activity of osteoclasts), and / or in the inhibition of bone resorption; their use in connection with treatment of bone disorders, such as conditions mediated by osteoclasts (e.g., increased osteoclast activity) and / or characterised by (e.g., increased) bone resorption, such as osteoporosis (e.g., osteoporosis not associated with inflammation; e.g., osteoporosis associated with a genetic predisposition, sex hormone deficiency, or ageing), cancer associated bone disease, and Paget's disease of bone.

The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array, and in particular a RANKL protein, RANKL fragment or RANKL peptide-VLP-array. More specifically, the invention provides a composition comprising a virus-like particle and at least one RANKL protein, RANKL fragment or RANKL peptide bound thereto. The invention also provides a process for producing the conjugates and the ordered and repetitive arrays, respectively. The compositions of the invention are useful in the production of vaccines for the treatment of bone diseases and as a pharmaccine to prevent or cure bone diseases and to efficiently induce immune responses, in particular antibody responses. Furthermore, the compositions of the invention are particularly useful to efficiently induce self-specific immune responses within the indicated context.

Cationic steroidal antimicrobials (“CSAs” or “ceragenins”) and methods of making and using the same. Particularly advantageous uses include treating infections in patient and sub-patient populations, especially those having a bone disease, a broken bone, a bone infection, or a bone implant.

A method for transdermal administration of parathyroid hormone by iontophoresis, which comprises applying electric current at least 2 times a day, which method is repeated one to four times each week, or an apparatus for the iontophoresis can be widely applied for not only the prevention or treatment of osteoporosis but also for general bone diseases which require promotion of bone morphogenesis, for example, treatment of ordinary fractures.The method of the present invention produces excellent pharmacological effects such as few side effects and a high bioavailability in long term administration for the prevention and treatment of bone diseases.

A novel polypeptide, osteoprotegerin binding protein, involved in osteoclast maturation has been identified based upon its affinity for osteoprotegerin. Nucleic acid sequences encoding the polypeptide, or a fragment, analog, or derivative thereof, vectors and host cells for production, and binding assays are described. Antibodies specifically binding osteoprotegerin binding protein are also described. Compositions and methods for the treatment of bone diseases such as osteoporosis, bone loss due to arthritis or metastasis, hypercalcemia, and Paget's disease are also provided.

The invention relates to an exosome derived from human pluripotent stem cells, a preparation based on the exosome and use of the exosome and preparation, and belongs to the technical fields of cell biology, molecular biology and drug research and development. The human pluripotent stem cell exosome or the preparation based on the human pluripotent stem cell exosome has the uses of A, being an additive cultured in vitro for maintaining the stemness of adult stem cells and inhibiting the senility of the adult stem cells; B, being an additive cultured in vitro for maintaining the proliferative activity of various tissue primary culture cells; C, being applied in preparing medicine for treating bone and cartilage degenerative changes; D, being applied in preparing medicine for preventing the bone and cartilage degenerative changes; E, being applied in preparing medicine for treating orthopedic diseases such as osteonecrosis, bone nonunion, fractures, cartilage injuries, tendon injuries, frozen shoulders or tendon adhesion. Compared with the prior art, the exosome secreted by the pluripotent stem cells has powerful functions of promoting tissue cell regeneration, preventing senility andtreating bone diseases.