145 results about "Transthyretin" patented technology

Described herein are methods and compositions for treating certain retinol-related diseases and conditions by modulation of transthyretin (TTR) and retinol binding protein (RBP) availability in the subject. For example, the methods and compositions provide for therapeutic agents for the treatment and / or prevention of age-related macular degeneration and / or dystrophies, metabolic disorders, idiopathic intracranial hypertension, hyperostosis, and protein misfolding and aggregation diseases. The compositions disclosed may be used as single agent therapy or in combination with other agents or therapies. In addition, described herein are methods and assays for selecting appropriate agents that can modulate the TTR and RBP availability in a subject.

Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

Compounds, compositions and methods are provided for modulating the expression of transthyretin in the brain, specifically the choroid plexus. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided.

The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying ovarian cancer status as well as endometrical cancer status in a patient. In particular, it has been found that hepcidin is a biomarker for both ovarian cancer and endometrial cancer and that a panel of biomarkers, including hepcidin, transthyretin and optionally other markers are useful to classify a subject sample as ovarian cancer or non-ovarian cancer. The biomarkers can be detected by SELDI mass spectrometry.

The present invention provides protein-based biomarkers and biomarker combinations that are useful in qualifying ovarian cancer status as well as endometrical cancer status in a patient. In particular, it has been found that hepcidin is a biomarker for both ovarian cancer and endometrial cancer and that a panel of biomarkers, including hepcidin, transthyretin and optionally other markers are useful to classify a subject sample as ovarian cancer or non-ovarian cancer. The biomarkers can be detected by SELDI mass spectrometry.

Methods and compositions for expressing a gene or nucleotide sequence of interest are provided. The compositions include an expression cassette that includes a synthetic enhancer, a transthyretin promoter, and a nucleotide sequence operably under the control of the synthetic enhancer and the transthyretin promoter. The expression cassette may be used in an adeno-associated viral (AAV) vector, such as a self-complementary AAV vector.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

A method for quantifying a neurodegenerative disorder in a patient that includes obtaining a fluid sample from the subject; measuring a protein biomarker complex in said fluid sample and correlating the measurement with mild cognitive impairment or Alzheimer's disease status. The biomarkers include those that comprise at least one of a transthyretin protein and / or a prostaglandin-H2 D-isomerase protein, and at least one second, different protein selected from a transthyretin, prostaglandin-H2 D-isomerase, beta-2-microglobulin, cystatin C, superoxide dismutase [Cu—Zn], plasma retinol-binding protein, phosphatidylethanolamine-binding protein, carbonic anhydrase 2, prostaglandin-H2 D-isomerase, and / or serotransferrin protein;

A method for treating a disease characterized by excessive lipofuscin accumulation in the retina of a mammal afflicted therewith comprising administering to the mammal an effective amount of a transthyretin (TTR) ligand.

The present invention relates generally to a peripheral marker or markers of blood barrier integrity and methods of using same in the diagnosis, prognosis, and treatment of a variety of diseases. The peripheral marker(s) of the present invention are particularly useful in the differential diagnosis of diseased states. The preferred embodiments of the present invention relate to methods, compositions, kits, and assays useful in determining the integrity or permeability of either a blood CSF barrier or a blood brain barrier. The various embodiments of the present invention can be used to identify subjects at risk for developing a disease associated with increased permeability of the blood brain barrier, as well as to provide insight on the ability of an agent or agents to pass through the blood brain barrier. Embodiments of the present invention preferably involve the use of subject derived blood samples to determine the occurrence and level of circulating proteins indicative of blood brain barrier permeability or integrity. The embodiments of the present invention also provides screening methods for diagnosis, prognosis, susceptibility, or degree of permeability of penetration of the blood brain barrier by detecting the presence of serum Transthyretin either directly or through the use of antibodies.

The present invention provides compositions comprising anti-transthyretin antibodies. The compositions are particularly useful for diagnosis, prognosis and / or treatment of amyloid diseases or symptoms thereof.

Described herein are methods and compositions for the detection of transthyretin (TTR), retinol binding protein (RBP) and retinol complex formation. The methods and compositions described herein also provide for the screening of modulators of retinol-RBP-TTR complex formation. Furthermore, the methods and compositions provide for therapeutic agents for the treatment and / or prevention of age-related macular degeneration and / or dystrophies.

The invention provides antibodies that specifically bind transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.

The present invention relates to a method for diagnosing a subject's Alzheimer's disease state. The method involves providing a database containing information relating to protein expression levels associated and not associated with Alzheimer's disease. The database includes information relating to at least a majority of the following proteins: albumin, alpha-1-antitrypsin, apolipoprotin E, apolipoprotein J, complement component 3, contactin, fibrin beta, Ig heavy chain, Ig light chain, neuronal pentraxin receptor, plasminogen, proSAAS, retinol-binding protein, transthyretin, and vitamin D binding protein. Information relating to proteins found in one or more cerebrospinal fluid samples from a subject is also provided and a database is used to analyze the information from the subject to diagnose the subject's Alzheimer's disease state. Also disclosed is a computer readable medium and a system, both useful in carrying out the present invention.

Transthyretin (TTR), a tetrameric thyroxine (T4) carrier protein, is associated with a variety of amyloid diseases. Derivative of biphenyl ethers (BPE), which are shown to interact with a high affinity to its T4 binding site thereby preventing its aggregation and fibrillogenesis. They prevent fibrillogenesis by stabilizing the tetrameric ground state of transthyretin. Two compounds (2-(5-mercapto-[1,3,4]oxadiazol-2-yl)-phenol and 2,3,6-trichloro-N-(4H-[1,2,4]triazol-3-yl) exhibit the ability to arrest TTR amyloidosis. The dissociation constants for the binding of BPEs and compound 11 and 12 to TTR correlate with their efficacies of inhibiting amyloidosis. They also have the ability to inhibit the elongation of intermediate fibrils as well as show nearly complete (>90%) disruption of the preformed fibrils. Biphenyl ethers and compounds 11 and 12 as very potent inhibitors of TTR fibrillization and inducible cytotoxicity.

The invention relates to methods of diagnosing or monitoring a psychotic disorder in a subject comprising providing a test biological sample from the subject, performing spectral analysis on said test biological sample to provide one or more spectra, and, comparing the one or more spectra with one or more control spectra. The invention also relates to methods for diagnosing or monitoring psychotic disorders such as schizophrenic or bipolar disorders, comprising measuring the level of one or more biomarkers present in a biological sample taken from a test subject, said biomarkers being selected from the group consisting of transthyretin, ApoA1, VLDL, LDL and aromatic species such as plasma proteins. The invention also relates to sensors, biosensors, multi-analyte panels, arrays, assays and kits for performing methods of the invention.

The invention relates to a method of diagnosis of Huntington's Disease in a diagnostic sample of a valid body tissue taken from a human subject, which comprises detecting an altered concentration of a protein in the diagnostic sample, compared with a sample of a control human subject, the protein being selected from: Swiss Prot accession number: Protein name; P10909: Clusterin precursor; P00738: Haptoglobin precursor; P01009: Alpha-1-antitrypsin precursor; P01024: Complement C3 precursor; P01620: 1 g kappa chain V-III region; P01834: 1 g kappa chain C region P01842: 1 g lambda chain C regions; P01857: 1 g gamma-1 chain C region; P01859: Ig gamma-2 chain C region; P01876: 1 g alpha-1 chain C region P02647: Apolipoprotein A-I precursor; P02649: Apolipoprotein E precursor; P02652: Apolipoprotein A-II precursor; P02655: Apolipoprotein C-II precursor; P02656: Apolipoprotein C-II precursor P02671: Fibrinogen alpha / alpha-E chain precursor; P02763: Alpha-1-acid glycoprotein 1 precursor; P02766: Transthyretin precursor; P02768: Serum albumin precursor; P02787: Serotransferrin precursor; P04196: Histidine-rich glycoprotein precursor; P06727: Apolipoprotein A-IV precursor; P19652: Alpha-1-acid glycoprotein 2 precursor; P68871 / P02042: Hemoglobin beta chain / Hemoglobin delta chain; P60709: Beta actin.

The present invention relates to a tumor marker for diagnosis of ovarian cancer, which is selected from the group consisting of alectin-1, cathepsin B, MHC class I antigen, heat shock protein (HSP) 27, ubiquitin carboxy-termal esterase L1, cellular retinol-binding protein (CRBP), transthyretin, SH3 binding glutamate-rich protein, tubulin-specific chaperone A, RNA binding protein regulatory subunit, γ-actin, tropomyosin and calcium / calmodulin-stimulated cyclic nucleotide phosphatase. The ovarian cancer is diagnosed effectively and efficiently based on detecting the expression levels of the tumor markers in the invention from the ovarian tissue sample of an individual to be diagnosed.

Provided are novel human-derived antibodies specific for transthyretin (TTR), preferably capable of binding misfolded, misassembled, and / or aggregated TTR species, as well as methods related thereto. In addition, methods of diagnosing and / or monitoring diseases and treatments thereof which are associated with TTR amyloidosis are provided. Assays and kits related to anti-bodies specific for TTR or TTR deposits and aggregates are also disclosed. The novel anti-TTR antibodies can be used in pharmaceutical and diagnostic compositions for TTR targeted immunotherapy and diagnostics.

The invention provides antibodies that specifically bind to transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.

The invention provides antibodies that specifically bind to transthyretin (TTR). The antibodies can be used for treating or effecting prophylaxis of diseases or disorders associated with TTR accumulation or accumulation of TTR deposits (e.g., TTR amyloidosis). The antibodies can also be used for diagnosing TTR amyloidosis and inhibiting or reducing aggregation of TTR, among other applications.

The present invention relates generally to diagnostic methods, systems, assays and kits for identification of subjects with cardiac amyloid deposits, where a low level of clusterin protein in a peripheral fluid sample, e.g., a serum sample from the subject, indicates the subject likely has cardiac amyloid deposits. Other aspects relate to methods of treatment of diseases or disorders characterized by cardiac amyloid deposits and transthyretin (TTR) amyloidosis, and more particularly to methods of treatment of cardiac-related amyloidosis and cardiac amyloid deposits in subjects with familial transthyretin (TTR), senile systemic amyloidosis (SSA), or familial amyloidodic polyneuropathy (FAP), or immunoglobulin light chain (AL) amyloidosis. Other aspects relate to methods and compositions comprising clusterin (CLU) or a clusterin agent (e.g. an agonist of clusterin activity or a biologically active fragment or derivative thereof), and their use in methods to treat a disease or disorder characterized by transthyretin (TTR) amyloidosis, e.g. senile systemic amyloidosis (SSA) or familial amyloidodic polyneuropathy (FAP), and their use in methods to treat amyloidotic cardiomyopathy associated with transthyretin (TTR) amyloidosis.

Disclosed herein are compounds and compositions thereof which find use in increasing stability of proteins particularly proteins that tend to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of proteins and thereby decreasing aggregate formation by these proteins. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein.

The invention relates to a biomarker of Parkinson disease, in particular to a method used for detecting pathogeny of the Parkinson disease and identifying the biomarker of the Parkinson disease (PD).The invention also provides a kit used for diagnosing or monitoring PD. A proteinic isoform or a monomer or polymer form thereof can be used for early diagnosing vulnerable subjects who are possible to suffer from PD. For example, the increase of the level of monomer transthyretin (TTR) in serum or the reduction of the level of dipolymer TTR can be used as a tool for diagnosing and monitoring PD.