40 results about "Chondroitin sulfate proteoglycan" patented technology

The invention provides a method of promoting neuronal plasticity in the CNS of a mammal, the method comprising administering to the CNS of the mammal an agent that reduces the inhibitory properties of chondroitin sulphate proteoglycans. Preferred agents are chondroitinases and sulfatases, e.g., chondroitinase ABC. Also provided are methods of identifying further agents.

The invention relates to the discovery of a novel Chondroitinase Glycoproteins (CHASEGP's), methods of manufacture, and potential uses in conditions where removal of chondroitin sulfates may be of therapeutic benefit. Chondroitinase Glycoproteins require both a substantial portion of the catalytic domain of the CHASEGP polypeptide and asparagine-linked glycosylation for optimal chondroitinase activity. The invention also includes carboxy-terminal deletion variants of CHASEGP that result in secreted variants of the protein to facilitate manufacture of a recombinant CHASEGP. Further described are suitable formulations of a substantially purified recombinant CHASEGP glycoprotein derived from a eukaryotic cell that generate the proper glycosylation required for its optimal activity. CHASEGP is useful for the degradation of glycosaminoglycans and chondroitin sulfate proteoglycans under clinical conditions where their removal is of therapeutic value.

Neural outgrowth in the central nervous system is achieved by administering chondroitinase AC and / or chondroitinase B to degrade chondroitin sulfate proteoglycans that inhibit or contribute to the inhibition of nervous tissue regeneration.

A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

Oligosaccharides, and in particular disaccharides, which are degradation products of chondroitin sulfate proteoglycan are effective for use in treating, inhibiting, or ameliorating the effects of injuries or diseases or disorders that result in or are caused by neuronal degeneration or of disorders resulting in mental and cognitive dysfunction. They are also useful for promoting neurogenesis.

The invention relates to a preparation method of composite hydrogel with an interpenetrating network structure. The preparation method comprises the following process steps of: (1) preparing a collagen solution with acetic acid, and preparing methacrylated chondroitin sulfate solution and methacrylated hyaluronic acid solution with deionized water, distilled water or phosphate buffer solution; (2) adjusting the pH value of the collagen solution prepared in the step (1) to 7.0-7.4 with sodium hydroxide solution under stirring at normal pressure and 0-4 DEG C, then adding the methacrylated chondroitin sulfate solution and methacrylated hyaluronic acid solution prepared in the step (1) to the collagen solution under stirring, uniformly mixing three solutions, then adding phosphate buffer solution for diluting until the collagen concentration in the mixed solution is 5-9mg / mL, then adding an initiator and a catalyst, and uniformly mixing to form a precursor solution; and (3) injecting theprecursor solution prepared in the step (2) to a mold, and placing the mold holding the precursor solution in an environment of normal pressure and 37 DEG C for 30-60minutes.

The invention discloses a tissue engineering nerval stent and a preparation method and an application thereof. The chemical extraction method is adopted for removing main antigens, namely cells, axons and myelin sheaths, which can cause the rejection, and chondroitinase ABC is further adopted for removing chondroitin sulfate proteoglycan in xenogeneic nerves, thereby getting acellular xenogenic nerves with a complete vessel of a basilar membrane of an extracellular matrix and can be used as the tissue engineering nerval stent. The tissue engineering nerval stent is applicable to restoring peripheral nerve defect of rats, rabbits, dogs, human beings and the like, plays a very obvious role in promoting the regeneration of the axons and can further increase the length of restoring the peripheral nerve defect, thereby being a great nerve transplantation medical material.

The present invention examined the accumulation of chondroitin sulfate proteoglycans (CSPGs). The present invention relates to neurodegeneration-suppressing agents that are suitable for gene therapy or prevention of neural fibrotic degenerative diseases which induce neural cell death due to an accumulation of abnormal proteins, where the therapies are based on siRNAs against N-acetylgalactosamine-4-O-sulfotransferases (N-acetylgalactosamine-4-O-sulfotransferase-1, N-acetylgalactosamine-4-O-sulfotransferase-2, and N-acetylgalactosamine-4-sulfate 6-O-sulfotransferase (GalNAc4ST-1, GalNAc4ST-2, and GALNAC4S-6ST, respectively)), which are sulfotransferases for acetylgalactosamine, a CSPG side chain, and chondroitinase ABC, an enzyme that degrades chondroitin sulfate, another CSPG side chain.

A method of promoting neural cell regeneration is carried out by contacting a neural cell with a compound that inhibits the binding of a chondroitin sulfate proteoglycan (CSPG) to a cellular (e.g., trans-membrane) PTPσ protein. The neural cell is associated with an injury or neurodegenerative condition.

The present inventors discovered for the first time that intestinal inflammation could be efficiently suppressed by suppressing the production or accumulation of chondroitin sulfate proteoglycans. Specifically, inflammation in the large intestine can be suppressed by using siRNA to suppress the expression of versican, which is one of the chondroitin sulfate proteoglycans. Compounds used as siRNA, such as nucleic acids, can be used as effective agents for suppressing intestinal inflammation. Furthermore, the above finding also suggests that such intestinal inflammation-suppressing agents can be found by screening for compounds that suppress the production or accumulation of chondroitin sulfate proteoglycans.

The present invention relates to hepatic fibrosis-suppressing agents that are suitable for treating or preventing fibrotic liver diseases such as cirrhosis, which comprise as an active ingredient a substance that inhibits the production or accumulation of chondroitin sulfate proteoglycans including chondroitinase ABC and ADAMTS-4; and methods of screening for the agents.The present inventors discovered for the first time that hepatic fibrosis could be efficiently suppressed by suppressing the production or accumulation of chondroitin sulfate proteoglycans. Specifically, fibrosis of liver tissues can be suppressed by administering chondroitinase ABC, a chondroitin sulfate proteoglycan-degrading enzyme, or by using siRNA to suppress the expression of C4ST-1, C6ST-1, or C6ST-2, a sulfotransferase for chondroitin sulfate proteoglycans. Compounds such as nucleic acids that are used as siRNA can be used as effective agents for suppressing hepatic fibrosis. Furthermore, hepatic fibrosis-suppressing agents can be found by screening for compounds that suppress the production or accumulation of chondroitin sulfate proteoglycans.

A method of perlecan isolation (from the EHS tumor) which produces “clean” (i.e. substantially “pure”) perlecan is disclosed. Clean perlecan is thus produced in sufficient quantities for use in a number of different in vitro and in vivo assays. In addition, this isolation method exploits a newly discovered aggregating property of a ˜220 kDa heparan sulfate proteoglycan (HSPG) observed during gel filtration chromatography, which allows it to be effectively separated from non-aggregating perlecan. The method employs specific cation exchange, anion exchange, molecular sieve chromatography and immobilized GAG affinity chromatography. It is demonstrated that there are no other contaminating proteins in the perlecan and HSPG preparations, and that the perlecan core protein is intact. Improved, clean perlecan based, rodent models of fibrillar amyloid protein deposition, accumulation and / or persistence in tissues are disclosed.

Polypeptides of the neuregulin (NRG) heparin binding domain (N-HBD) and nucleic acids coding therefor are disclosed. In particular, fusion polypeptides are produced that comprise, as a targeting structure, a N-HBD polypeptide, fragment, homologue or functional derivative and a protein to be targeted. This is fused to a polypeptide or peptide being targeted (Ptrg) to cell surfaces rich in heparan sulfate proteoglycans to either activate or inhibit interactions at tyrosine kinase receptors. Such products are used to treat diseases or conditions where either agonism or antagonism at tyrosine kinase receptors has beneficial effects, including cancer and a multitude of diseases of the nervous system.

This invention provides methods and compositions for reducing chondroitin-sulfate-proteoglycan-mediated inhibition of neuronal growth. The methods and compositions provided herein are particularly useful for treatment of neuronal damage or degeneration.

Human antibody fragments against chrondroitin sulfate proteoglycan 4 can be used to deliver cytotoxic agents to cells which express CSPG4. The agents can be diagnostic or therapeutic moieties. They may be linked by covalent or non-covalent linkages to the antibody fragments. They may be produced as a genetic fusion product or joined together synthetically, for example. When the human antibody fragments are internalized by the cells to which they bind, they can carry with them the attached agents. Thus toxic agents having intracellular targets have enhanced killing upon internalization.

A composition having tissue repair activity, which is capable of promoting reactions associated with tissue repair, contains at least one selected from the group consisting of a first component that is a protein having a monocyte chemotactic protein-1 (MCP-1) activity, a second component that is a protein having the extracellular domain activity of sialic acid-binding immunoglobulin-type lectin-9 (Siglec-9), and a third component that is at least one of chondroitin sulfate and chondroitin sulfate proteoglycan.

The invention relates to intelligent thermo-sensitive glycosyl hydrogel with a dumbbell structure and a preparation method of the hydrogel. The whole structure of the hydrogel is dumbbell-shaped, small molecular chondroitin sulfate proteoglycans are used as raw materials in preparation, a glycosyl monomer containing polymerizable double bonds is firstly synthesized by means of esterification and etherification reaction, and then double thioester serving as a chain transfer agent is polymerized with an N-alkyl acrylamide thermo-sensitive monomer by a reversible addition fragmentation chain transfer agent free radical polymerization method to prepare the novel intelligent glycosyl hydrogel with the dumbbell structure. The hydrogel has the advantages that the structure can be controlled, the molecular weight of the hydrogel is between that of supramolecular gel and that of polymer gel, the shortcomings of the supramolecular gel and the polymer gel are overcome, carbohydrates are used as raw materials, and the hydrogel serving as a natural biomass resource has fine biocompatibility, biodegradability, non-toxicity, no stimulation and the like that petrochemical raw materials do not have.

The invention relates to a star-shaped polyester compound and a preparation method thereof, which relate to the field of polymer materials. The preparation method is characterized by adopting chondroitin sulfate proteoglycans as a chain transfer center, carrying out ring-opening polymerization reaction on a cyclic ester monomer under the catalysis of an organic metal catalyst, and thus high-efficiently obtaining the polyester compound with a star-shaped topology structure with a high conversion rate. The preparation method is cheap and easy-to-get in raw materials, convenient and practical inoperation, and suitable for large-scale industrial production. The length of a branch chain of the star-shaped polyester compound can be controlled through adjusting a feeding ratio, so that a betterpractical value is achieved. According to the star-shaped polyester compound prepared by adopting the preparation method of the star-shaped polyester compound, the hydrophily is increased, the mechanical property is improved, the molecular weight is controllable, and the star-shaped polyester compound can be used as a raw material of a macromolecule drug carrying microsphere so as to have a greatapplication prospect.

The present invention relates to melanoma-associated chondroitin sulfate proteoglycan (MCSP) epitopes recognized by T cells, especially by CD4+ T lymphocytes (short T-cells) and CD8+ T cells, on human melanoma cells. In more detail, the present invention relates to novel T-cell stimulatory tumour antigenic peptides corresponding to said epitopes (MCSP peptides); to fusion proteins comprising said MCSP peptides; to the use of said MCSP peptides, fusion proteins or of the full length MCSP protein itself or fragments thereof to induce an immune response, especially a T-cell response; to the use of said MCSP peptides, fusion proteins or full length MCSP protein itself or fragments thereof to prepare immune cells, such as mature dendritic cells (DCs) loaded with anyone of the peptides according to the invention, or peptide-specific T-cell clones, especially CD4+ or CD8+ T cell clones; to the use of said MCSP peptides, fusion proteins or MCSP itself or fragments thereof for research and development on / of a cancer treatment; to the use of said MCSP peptides, fusion proteins or MCSP itself or fragments thereof for preparing a medicament for inducing a T cell response in a patient, preferably for the treatment of cancer, more preferably for the treatment of melanoma, including cutaneous and ocular melanoma, and other MCSP expressing tumours such as breast cancer, notably lobular breast carcinoma, astrocytoma, glioma, glioblastoma, neuroblastoma, sarcoma and certain types of leukaemia; to the use of said MCSP peptides, fusion proteins or full length MCSP protein or fragments thereof for the preparation of a medicament, and a diagnostic agent for the treatment and prophylaxis as well the diagnosis of an immune response against tumours; and to the use of said peptide-specific T-cell clones for diagnosing or treating cancer.

A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

The present invention provides methods of increasing the half-life factor VIII. More specifically, the invention methods of increasing the half-life of factor VIII by substituting amino acids in the A2 domain or in the C2 domain of factor VIII or in both domains. It further provides factor VIII mutants produced by these methods. The invention also provides a method of using receptor-associated protein (RAP) to increase the half-life of factor VIII. The invention also provides polynucleotides encoding the mutant factor VIII, polynucleotides encoding RAP, and methods of treating hemophilia using the polypeptides and polynucleotides of the invention.

A nucleic acid molecule encoding a chimeric chondroitin sulfate proteoglycan 4 (CSPG4) protein, wherein the chimeric CSPG4 protein comprises, from the N-terminal to the C-terminal: i) a first portion derived from the human CSPG4 sequence and a second portion derived from the canine CSPG4 sequence or ii) a first portion derived from the canine CSPG4 sequence and a second portion derived from the human CSPG4 sequence.

The use of a cancerous disease modifying antibody (CDMAB) 11 BD-2E11-2 for treating a tumor in humans and methods of isolating and identifying cancerous cells which express a melanoma-associated chondroitin sulfate proteoglycan (MCSP) antigenic moiety. The monoclonal antibody 11 BD-2E11-2 (ATCC accession number PTA-5643), which binds a MCSP antigenic moiety, is cytotoxic to cancer cells which express the antigenic moiety. The monoclonal antibody 11 BD-2E11-2 is useful for delaying the disease progression of a human tumor.

The disclosure features compositions and methods that may be used to detect the presence of tumor cell-derived exosomes in a patient (e.g., a human patient) having cancer. The compositions and methods described herein may also be used to evaluate the patient's prognosis, as well as monitor the likelihood of the patient to benefit from therapy, such as immunotherapy. The disclosure also features antibodies that specifically bind chondroitin sulphate proteoglycan 4 (CSPG4), as well as antigen-antibody complexes containing the same.

The invention discloses a porous injectable calcium phosphate bone cement compound. A chondroitin sulfate particle is used as a pore-foaming agent, and is uniformly mixed with solid-phase calcium phosphate bone cement; afterwards, an obtained mixture is uniformly mixed and agitated with liquid-phase calcium phosphate bone cement, so that the porous injectable calcium phosphate bone cement compoundis obtained, wherein the amount of the chondroitin sulfate particle accounts for 10 to 30 percent of the total mass of the solid-phase calcium phosphate bone cement and the chondroitin sulfate particle. The porous injectable calcium phosphate bone cement compound prepared by the invention has the internal pore size of 10 to 50 microns and the porosity reaching approximately 60 percent, can be used for forming favorable pore connectivity, is used for accelerating the degradation of bone cement, further, has favorable biocompatibility and bone repair capacity, and can be used as a novel bionicbone repair material for bone tissue of a human body.