54 results about "Hemochromatosis" patented technology

Modulation of iron homeostasis by regulating BMP-6 activity is provided. Methods of using BMP-6 and BMP-6 protein-specific reagents, such as antibodies, for altering serum iron levels in humans are provided. Such antibodies are useful in pharmaceutical compositions for the prevention and treatment of hemochromatosis and anemia of inflammation.

Positional cloning has been carried out to identify the gene responsible for the hypochromic anemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a novel multiple-transmembrane domain protein, expressed in the yolk sac. Zebrafish ferroportin1 is required for the transport of iron from maternally-derived yolk stores to the circulation, and functions as an iron exporter when expressed in Xenopus oocytes. Human and mouse homologs of the ferroportin1 gene have been identified. The invention includes isolated polynucleotides, vectors and host cells comprising nucleotide sequences encoding Ferroportin1 proteins and variants thereof, including those having iron transport function. The invention also includes polypeptides encoded by ferroportin1 genes and variants of such polypeptides, and fusion polypeptides comprising a Ferroportin1 or a portion thereof. Methods to produce a Ferroportin1, methods to produce antibodies to a Ferroportin1 and methods to identify agents binding to a Ferroportin1, which can be inhibitors or enhancers of Ferroportin1 iron transport activity, are also described. Inhibitors of Ferroportin1 activity can be used in a therapy for hemochromatosis.

Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, eg. a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, a inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding ageing, and prevention and / or treatment of skin ageing and skin protection against sunlight and / or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety, the neuroprotective function is imparted to the compound e.g. by a neuroprotective peptide, and a combined antiapoptotic and neuroprotective function by a propargyl group.

Positional cloning has been carried out to identify the gene responsible for the hypochromic anemia of the zebrafish mutant weissherbst. The gene, ferroportin1, encodes a novel multiple-transmembrane domain protein, expressed in the yolk sac. Zebrafish ferroportin1 is required for the transport of iron from maternally-derived yolk stores to the circulation, and functions as an iron exporter when expressed in Xenopus oocytes. Human and mouse homologs of the ferroportin1 gene have been identified. The invention includes isolated polynucleotides, vectors and host cells comprising nucleotide sequences encoding Ferroportin1 proteins and variants thereof, including those having iron transport function. The invention also includes polypeptides encoded by ferroportin1 genes and variants of such polypeptides, and fusion polypeptides comprising a Ferroportin1 or a portion thereof. Methods to produce a Ferroportin1, methods to produce antibodies to a Ferroportin1 and methods to identify agents binding to a Ferroportin1, which can be inhibitors or enhancers of Ferroportin1 iron transport activity, are also described. Inhibitors of Ferroportin1 activity can be used in a therapy for hemochromatosis.

The present invention provides new systems and strategies for the regulation of iron metabolism in mammals. In particular, methods of using agonists and antagonists of TGF-β superfamily members to modulate the expression or activity of hepcidin, a key regulator of iron metabolism, are described. The inventive methods find applications in the treatment of diseases associated with iron overload, such as juvenile hemochromatosis and adult hemochromatosis, and in the treatment of diseases associated with iron deficiency, such as anemia of chronic disease and EPO resistant anemia in end-stage of renal disease. The present invention also relates to screening tools and methods for the development of novel drugs and therapies for treating iron metabolism disorders.

Polynucleotide and polypeptide sequences for HFE2A, as well as mutations associated with juvenile hemochromatosis, and methods of utilizing these for the screening and identification of agents for the treatment of diseases of iron metabolism, including small organic compounds, are disclosed along with methods of treating and / or ameliorating diseases of iron metabolism, especially in human patients are disclosed. Diagnostic compounds, kits and methods using HFE2A are also described.

Modulation of iron homeostasis by regulating BMP-6 activity is provided. Methods of using BMP-6 and BMP-6 protein-specific reagents, such as antibodies, for altering serum iron levels in humans are provided. Such antibodies are useful in pharmaceutical compositions for the prevention and treatment of hemochromatosis and anemia of inflammation.

New diagnostic parameters or indexes for detection of absolute iron deficiency, latent iron deficiency, functional iron deficiency, or latent functional iron deficiency have been disclosed. The parameters include a RBC size factor, RSf1 defined by the formula of (MCV×MRV)1 / 2, or RSf2 defined by the formula of (MCV×MRV) / 100, a volume-hemoglobin factor (VHf) defined by the formula of (MCV×Hgb) / 100, and a volume-hemoglobin / distribution factor (VHDWf) defined by the formula of (MCV×Hgb) / (RDW×10). Further disclosed are the methods of using these parameters for detection of absolute iron deficiency, latent iron deficiency, functional iron deficiency, or latent functional iron deficiency. Also disclosed is a method of using RSf for detection of hemochromatosis.

Modulation of iron homeostasis by regulating BMP-6 activity is provided. Methods of using BMP-6 and BMP-6 protein-specific reagents, such as antibodies, for altering serum iron levels in humans are provided. Such antibodies are useful in pharmaceutical compositions for the prevention and treatment of hemochromatosis and anemia of inflammation.

The invention discloses a primer combination, method and kit for constructing a targeted library of multiple inherited metabolic liver diseases based on high-throughput sequencing. The base sequence of the primer combination is shown as SEQ ID No. 1 to SEQ ID No. 2245, and the primer combination covers total 703 exons and cutting regions of 43 genes such as SERPINA1, G6PC, SLC37A4, AGL and the like, and is capable of detecting 41 sub-type gene variation loci of totally 20 inherited metabolic liver diseases comprising alpha-1-antitrypsin deficiency, glycogen storage disease, citrullinemia, aminosuccinuria, hemochromatosis, porphyrinopathy, cystic fibrosis, bile acid synthesis defect, Gaucher disease, hereditary fructose intolerance, cholesterol ester storage disease, Gilbert syndrome, Dubinsyndrome, Rotor syndrome, progressive familial intrahepatic choleatasia and the like. The primer combination disclosed by the invention is simple in operation, high in accuracy and low in time consumption, and the time cost and manual cost used for detecting genes and fragments one by one during Sanger sequencing can be greatly saved.

The invention features a method of diagnosing an iron disorder, e.g., hemochromatosis, or a genetic susceptibility to developing such a disorder in a mammal by determining the presence of a mutation in exon 2 or in an intron of an HFE nucleic acid.

Disclosed herein are antisense compounds and methods for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and / or condition in an individual in need thereof. Iron accumulation diseases in an individual such as hemochromatosis or β-thalassemia can be ameliorated or prevented with the administration of antisense compounds targeted to TM-PRSS6.

The invention discloses a kit for simultaneously detecting various inherited metabolic liver diseases. The kit is a PCR detection kit and comprises a PCR reaction system reagent, a primer and a positive control group. The genetic locus detected by the kit comprises a hyperbilirubinemia genetic locus, a wilson disease genetic locus and / or hemochromatosis genetic locus. The kit disclosed by the invention has the beneficial effects that a molecular biological technique is utilized to establish a convenient, sensitive and reliable clinical test platform for the relatively backward diagnosis and treatment level for the inherited metabolic liver diseases at present stage in China and various common inherited metabolic liver diseases can be diagnosed and identified at one time within a shorter period of time.

The invention discloses a primer composition, a kit and a method for detecting susceptibility gene mutation of hemochromatosis and hepatolenticular degeneration. The invention firstly discloses the primer composition for detecting the susceptibility gene mutation of hemochromatosis and hepatolenticular degeneration. The invention further discloses the kit containing the primer composition and themethod for detecting the susceptibility gene mutation of hemochromatosis and hepatolenticular degeneration. The method for detecting the susceptibility gene mutation of hemochromatosis and hepatolenticular degeneration integrates gene mutation and copy number mutation information of all exon and intron cleavage regions of susceptibility genes of hemochromatosis and hepatolenticular degeneration inChinese population, and has the advantages of high detection flux, high specificity and sensitivity, 100% of sequencing coverage, more than 30x of depth, clear and objective gene detection result interpretation, good accuracy and repeatability, low cost, simple operation and easy popularization; and the method can not only detect known high-incidence mutation, but also discover new mutation sites.

Disclosed herein is a method for treating hepatic fibrosis comprising administering to a patient in need of such treatment an amount effective to treat hepatic fibrosis of imatinib mesylate. This is based on the ability of imatinib mesylate to down regulate stellate cell activation in culture and in vivo. Hepatic fibrosis is not limited to patients with chronic Hepatitis B, Hepatitis C, non-alcoholic steatophepatitis (NASH), alcoholic liver disease, metabolic liver diseases (Wilson's disease, hemochromatosis), biliary obstruction (congenital or acquired) or liver diseases associated with fibrosis of unknown cause.

The present invention provides a substantially purified carbohydrate ligand that specifically binds to a leczyme. The invention also provides methods to identify a carbohydrate ligand that specifically binds to a leczyme or a leczyme that specifically binds to a carbohydrate ligand. The invention further provides methods to identify a peptide that binds to the carbohydrate ligand binding site of a leczyme. The present invention provides methods to isolate a carbohydrate ligand or a leczyme and to identify a carbohydrate ligand or a leczyme that modifies the function of a cell and to obtain such functionally modified cells. The invention further provides methods to modify a cell to express a carbohydrate ligand by introducing an expression vector encoding a leczyme into the cell. The invention also provides methods to modulate the immune response to an antigen by administering the antigen and a carbohydrate ligand. In addition, the invention further provides methods to treat a disease state involving a leczyme by administering a carbohydrate ligand that binds the leczyme or by administering a leczyme that has a similar binding specificity to the leczyme involved in the disease state. The invention further provides methods to diagnose a genetic basis for hemochromatosis by detecting a mutation in a class I MHC molecule that reduces it's ability to associate with beta2 microglobulin.

Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and / or condition in an individual in need thereof. Iron accumulation diseases in an individual such as polycythemia, hemochromatosis or β-thalassemia can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to TMPRSS6.

The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the TMPRSS6 gene expression or inhibits its expression and therapeutic uses such as for the treatment of hemochromatosis, porphyria and blood disorders such as β-thalassemias, sickle cell disease and transfusional iron overload or myelodysplastic syndrome.