897 results about "Lysosome" patented technology

A method of enhancing the activity of lysosomal alpha-Galactosidase A (alpha-Gal A) in mammalian cells and for treatment of Fabry disease by administration of 1-deoxy-galactonojirimycin and related compounds.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Disclosed herein are novel peptide linkers and polypeptide compositions comprising the linkers (e.g., chimeric polypeptides) and methods of using the polypeptide compositions. The compositions and methods are particularly useful for targeting / delivering a polypeptide or protein of interest (e.g., a therapeutic polypeptide) to a cell, tissue or organ of interest in order to treat various diseases or disorders (e.g., lysosomal storage disorders).

Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.

Methods and compositions for treating or preventing microbial infection in mammals with sulfated polysaccharides wherein the polysaccharides have a degree of sulfation effective to enable maximal interaction of constituent sulfate groups with the microbe which causes the infection and wherein the sulfated polysaccharide is not substantially endocytosed or degraded by cell receptor binding in the mammal and thereby retains antimicrobial activity in vivo.

A post-incubation treatment is employed to effectively remove targets, such as proteins / protein complexes, or other label-bearing moieties that may non-specifically bind to a microarray substrate during a binding assay. Following incubation, a one-step wash is carried out with a liquid containing digester, e.g., a digestive enzyme (protease) or lysosome, which is effective to remove non-specifically bound targets or at least labeled portions of such targets from the substrate. Proteases are bound to or coated onto large molecules or onto solid particles of such a size such that they are prohibited from entering the porous surfaces of 3-D hydrogel microspots and are unable to reach and digest labeled target-probe complexes that are disposed within such porous hydrogel microspots. Digested segments of such protein which contain labels (or of essentially the entire protein) are carried away in the wash liquid and thus are not present to create background noise during imaging.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

The present invention is directed to methods and systems for the treatment of inborn genetic errors or other defects that cause deficiencies of active enzymes or proteins within the cells of the central nervous system. Such methods and systems generally comprise an implantable catheter system designed for the chronic delivery of specially formulated proteins to intrathecal, intracerebroventricular, and / or intraparenchymal regions of the central nervous system. The invention has application in the neuropathic aspects of the broad category of lysosomal storage diseases. These genetic based diseases are the result of insufficient enzyme activity to catabolize specific substances, which thereby accumulate in the cellular lysosomes.

Methods for eliciting in an animal in need thereof a cell-mediated immune response specific to an antigen, the method comprising providing an antigen preparation comprising particles on the surface of which the antigen is attached, and administering the antigen preparation to the animal, wherein the particles are taken up by antigen presenting cells (APC) of the animal via phagocytosis, forming a phagosome inside the APC, wherein the antigen is attached to the surface of the particle in such a way that the antigen is released in the phagosome before the phagosome fuses with a late endosome or a lysosome, and wherein the antigen is cross-presented on a Class I MHC molecule. Also provided are particulate antigen preparations or particulate vaccines that can be delivered to an animal in need thereof for vaccination against, for preventing or treating, a disease related to the antigen, such as cancer and a viral infection.

Described is a method for treating an individual having a neurological disorder with an associated mutation or mutations in a gene encoding a lysosomal enzyme. Specifically, the individual is administered a specific pharmacological chaperone for the lysosomal enzyme which increases trafficking of the protein from the ER to the lysosome in neural cells, with or without concomitantly increasing enzyme activity in neural cells. Restoration of trafficking relieves cell stress and other toxicities associated with accumulation of mutant proteins. Restoration of enzyme activity relieves substrate accumulation and pathologies associated with lipid accumulation. In a specific embodiment, the neurological disorder is Parkinson's disease or parkinsonism which is associated with mutations in glucocerebrosidase.

The present invention relates to a method for determining the delivery rates and / or efficiency of a siRNA, miRNA or related molecule to target organs or cells, a kit and the use of proteins or lipids involved in the formation of the endolysosomal system for modulating the activity and / or the cell-to-cell transfer of RNA, small RNA, for example miRNA, siRNA and piRNA, mRNA or non-coding RNA.It finds many applications in particular in methods for identifying the target(s) of miRNA or siRNA therapeutics, in methods for determining the efficiency of a treatment with siRNA and / or miRNA therapeutics, in methods for determining the efficiency of a treatment with siRNA and / or miRNA therapeutics, and in methods for genotyping and / or characterizing the condition of a person, a tumor or a fetus.

The present invention relates to methods for providing lysosomal enzymes to a subject by administering stem cells, preferably Multipotent Adult Progenitor Cells (MAPCs). The invention further relates to methods for treating lysosomal storage disorders by administering stem cells.

This invention provides compositions of active highly phosphorylated lysosomal sulfatase enzymes, their pharmaceutical compositions, methods of producing and purifying such lysosomal sulfatase enzymes and compositions and their use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the lysosomal sulfatase enzyme.

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

The present invention comprises methods and compositions for the treatment or alleviation of NAFLD (non-alcoholic fatty liver disease) and those conditions associated with NAFLD, including fatty liver disease, nonalcoholic steatohepatitis (NASH) and cirrhosis through the use of pharmaceutical formulations of lysosomal acid lipase or related proteins and / or polypeptides. This invention is also directed to a combination therapy treatment for treating The Metabolic Syndrome. As part of a combination therapy regime for the treatment of The Metabolic Syndrome, pharmaceutical formulations of lysosomal acid lipase or related proteins and / or polypeptides are used as part of the combination therapy regime for treating NAFLD (and NASH), which comprises one of the conditions constituting The Metabolic Syndrome,

This invention provides conjugates of therapeutic or active agents with melanotransferrin or with other ligands of a melanotransferrin receptor, melanotransferrin receptor modulators, and related compositions and methods for modulating blood-brain barrier transport by providing methods of screening and selecting such conjugates, ligands, and modulators in vitro and in vivo, and methods of use of such conjugates, modulators and ligands in diagnosis and the treatment of diseases, including particularly diseases of the central nervous system or lysosomal storage diseases.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

Methods of modulating uptake of extracellular lysosomal enzymes by administering a pharmaceutical agent and methods of treating a lysosomal storage disease (such as Gaucher disease, Pompe disease, Fabry disease or Niemann-Pick disease) or enhancing enzyme replacement therapy or gene therapy, comprising administering a pharmaceutical agent such as dexamethasone, glucose or insulin, are provided.

The invention relates to a liver targeting anticancer nanometer prodrug system basing on dendritic polymer, provides a method for preparing the prodrug system and the uses thereof and belongs to the technical field of biological medicine as well as the technical field of nano medicine. With the polyethylene glycol modified PAMAM treelike polymer of distal liver targeting group (T) as a carrier (T-PEG-PAMAM) and Doxorubicin (DOX) as treatment drug, the invention obtains the prodrug (T-PEG-PAMAM-DOX) through the covalent bond connection with degradable lysosome between the carrier and the Doxorubicin. The invention further provides the application of the liver targeting anticancer nanometer prodrug system basing on the dendritic polymer in the preparation of drugs for treating solid tumors. With the long-acting cycle in blood, the liver targeting anticancer nanometer prodrug system basing on the dendritic polymer can enhance the phagocytosis of hepatoma cells on polymers nano-micelles, realize the active and passive targeting on liver tumor tissues, improve the clinical efficacy and the bioavailability of present liver cancer therapeutic drugs and lower toxic and side effects.

There is disclosed an isolated, modified recombinant β-glucuronidase wherein the modification is having its carbohydrate moeties chemically modified so as to reduce its activity with respect to mannose and mannose 6-phosphate cellular delivery system while retaining enzymatic activity Also disclosed are methods for the treatment of lysosomal storage disease in mammals wherein the mammal is administered a therapeutically effective amount of isolated, modified recombinant β-glucuronidase whereby said storage diseased is relieved in the brain and visceral organs of the mammal. Also disclosed are other lysosomal enzymes within the scope of the invention.

The present invention relates to methods for providing lysosomal enzymes to a subject by administering stem cells, preferably Multipotent Adult Progenitor Cells (MAPCs). The invention further relates to methods for treating lysosomal storage disorders by administering stem cells.

Targeted therapeutics that localize to a specific subcellular compartment such as the lysosome are provided. The targeted therapeutics include a therapeutic agent and a targeting moiety that binds a receptor on an exterior surface of the cell, permitting proper subcellular localization of the targeted therapeutic upon internalization of the receptor. Nucleic acids, cells, and methods relating to the practice of the invention are also provided.

The invention provides a chimeric CNS targeting polypeptide having a BBB-receptor binding domain and a payload polypeptide domain. The chimeric CNS targeting polypeptide can have a BBB-receptor binding domain consisting of a receptor binding domain from ApoB, ApoE, aprotinin, lipoprotein lipase, PAI-1, pseudomonas exotoxin A, transferrin, α2-macroglobulin, insulin-like growth factor, insulin, or a functional fragment thereof. Nucleic acids encoding a chimeric CNS targeting polypeptide are also provided. Further provided is a method of delivering a polypeptide to the CNS of an individual. The method consists of administering to the individual an effective amount of a chimeric CNS targeting polypeptide, said chimeric CNS targeting polypeptide comprising a BBB-receptor binding domain and a payload polypeptide domain. The method also can deliver a polypeptide to the lysosomes of CNS cells.

The present invention provides improved formulations for lysosomal enzymes useful for enzyme replacement therapy. Among other things, the present invention provides formulations that preserve or enhance the stability and / or efficacy of a lysosomal enzyme such as acid alpha-glucosidase.

This invention provides compositions of active highly phosphorylated lysosomal sulfatase enzymes, their pharmaceutical compositions, methods of producing and purifying such lysosomal sulfatase enzymes and compositions and their use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the lysosomal sulfatase enzyme.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m / II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.