93 results about "Growth differentiation factor" patented technology

Modified and stabilized propeptides of Growth Differentiation Factor proteins, such as GDF-8 and Bone Morphogenetic Protein-11, are disclosed. Also disclosed are methods for making and using the modified propeptides to prevent or treat human or animal disorders in which an increase in muscle tissue would be therapeutically beneficial. Such disorders include muscle or neuromuscular disorders (such as amyotrophic lateral sclerosis, muscular dystrophy, muscle atrophy, congestive obstructive pulmonary disease, muscle wasting syndrome, sarcopenia, or cachexia), metabolic diseases or disorders (such as such as type 2 diabetes, noninsulin-dependent diabetes mellitus, hyperglycemia, or obesity), adipose tissue disorders (such as obesity), and bone degenerative diseases (such as osteoporosis).

The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject. The invention also provides a method of modulating the growth of muscle tissue or adipose tissue in a eukaryotic organism by administering an agent that affects myostatin signal transduction to the organism.

Modified and stabilized propeptides of Growth Differentiation Factor proteins, such as GDF-8 and Bone Morphogenetic Protein-11, are disclosed. Also disclosed are methods for making and using the modified propeptides to prevent or treat human or animal disorders in which an increase in muscle tissue would be therapeutically beneficial. Such disorders include muscle or neuromuscular disorders (such as amyotrophic lateral sclerosis, muscular dystrophy, muscle atrophy, congestive obstructive pulmonary disease, muscle wasting syndrome, sarcopenia, or cachexia), metabolic diseases or disorders (such as such as type 2 diabetes, noninsulin-dependent diabetes mellitus, hyperglycemia, or obesity), adipose tissue disorders (such as obesity), and bone degenerative diseases (such as osteoporosis).

A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and / or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue.

The present invention provides receptors for the growth differentiation factor (GDF) family of growth factors and methods of identifying such receptors. Also included are methods of identifying antibodies which bind to the receptors, peptide fragments of the receptor which inhibit GDF binding, GDF receptor-binding agents capable of blocking GDF binding to the receptor. The receptors of the invention allow the identification of antagonists or agonists useful for agricultural and human therapeutic purposes.

Provided herein are methods for the treatment of anemia, wherein the methods comprise administration of antagonists of Growth differentiation factor 11 (GDF1 1; also known as bone morphogenetic protein 11 (BMP11)) to a subject in need of the treatment.

Disclosed is a method for diagnosing melanoma in a human subject, as well as a method for providing a prognosis to a human subject who is at risk of developing melanoma recurrence, and a method for determining the stage of melanoma in a human subject, comprising the step of determining the level of expression of phosphatase and actin regulator 1 (PHACTR1) gene, or fragments thereof, either alone or in combination with the level of expression of secreted integrin-binding phosphoprotein (SPP1), preferentially expressed antigen in melanoma (PRAME), growth differentiation factor 15 (GDF 15), and chemokine C-X-C motif ligand 10 (CXCL10) genes. Further, the invention relates to a diagnostic kit, comprising at least one substance for detection of the expression of PHACTR1, or fragments thereof, either alone or in combination with the detection of SPP1, PRAME, GDF15, and CXCL10, for the diagnosis or prognosis of melanoma.

A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and / or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is provided. Also provided are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue and bone content.

Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

The invention discloses an SNP (Single Nucleotide Polymorphism) marker related to the litter size of a sow and application thereof. The SNP molecular marker provided by the invention is positioned on G+701C and T+4578C sites of a GDF2 (Growth Differentiation Factor 2). By designing the primers, the two obtained sequences are respectively positioned on Exons 1 and 2 of the gene GDF2 of the sow, the 701bp of the gene GDF2 (ENSSSCG00000010375) sequence recorded in the Ensemble database has one G701-C701 base mutation and results in the change (Ala-114-Pro) of the amino acid, and the 4578bp has one T4578-4578C base mutation which is a synonymous mutation. An RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) method is used for researching the polymorphism of the site. The invention provides a new marker for molecular marker-assisted selection of sows.

The present invention is concerned with a method for differentiating between liver fibrosis and liver cirrhosis in a subject based on the determination of growth differentiation factor 15 (GDF-15), hepatocyte growth factor (HGF) and / or endoglin in a sample of a subject and comparing the thus determined amount with a reference amount (reference amounts). Further envisaged by the present invention are kit and a device adapted to carry out the method of the present invention.

Disclosed is a method for diagnosing whether a subject suffers from a mild or severe form of liver cirrhosis based on determining the amount of GDF-15 (growth differentiation factor 15), PlGF (placental growth factor), and / or hepatocyte growth factor (HGF) in a sample from the subject and comparing the thus determined amount(s) with a reference amount (reference amounts). The method may further include determining the amount of adiponectin in a sample from the subject, and comparing the amount to a reference amount for adiponectin. Also described is a method to identifying a subject being susceptible to liver transplantation including determining the amount of GDF-15, PlGF, and / or HGF in a sample from the subject and comparing the thus determined amount(s) with a reference amount (reference amounts).

The invention discloses new applications of an antibody of GDF15 (Growth differentiation factor 15) protein. The invention provides the following three applications of the antibody of the GDF15 protein: 1. the application in preparing a reagent for assisting to identify a hepatitis C patient or a hepatitis B patient; 2. the application in preparing a reagent kit for assisting to identify the hepatitis C patient or the hepatitis B patient; and 3. the application in preparing a reagent kit for assisting to identify the hepatitis C progress of the hepatitis C patient, wherein the hepatitis C progress is chronic hepatitis C, hepatitis C cirrhosis or liver cancer. On the basis of the three applications, the antibody of the GDF15 protein can be prepared into three reagent kits. The reagent kit can be used for the serological diagnosis of viral hepatitis (the hepatitis C or the hepatitis B) and judging the disease progress (the chronic hepatitis C, the hepatitis C cirrhosis or the liver cancer) and for prognosis and viral hepatitis treatment monitoring and has great value for the diagnosis and the treatment of the hepatitis C and the hepatitis B.

Purified GDF-8 polypeptides of aquatic organisms.

Peptides (and derivatives thereof), topical compositions, and methods of diminishing signs of aging and / or improving health of human integuments are provided. The peptides are derived from human Growth Differentiation Factor 11 (GDF-11).

The present invention relates to methods for inhibiting myostatin, a regulator of muscle mass, for muscle enhancement (including inducing hypertrophy and / or hyperplasia) as well as improving muscle function (including decreasing atrophy and / or increasing endurance, force and / or strength). Some of the methods involve delivering genes to cells using viral vectors such as a recombinant Adeno-associated virus (rAAV), lentivirus or equine-associated virus, or using other delivery techniques known in the art in order to inhibit myostatin. Examples of genes to be delivered are genes encoding proteins such as Follistatin, Follistatin-related gene-1 (FLRG-1), growth differentiation factor associated protein-1 (GASP-1) and myostatin precursor propeptide. In other methods of the invention, expression of proteins such as activin IIb and myostatin is inhibited by oligonucleotide techniques to effect muscle enhancement. All the methods have applications in the treatment of musculoskeletal and neurodegenerative disorders among others, as well as enhancing muscle in livestock.

Disclosed is a method for diagnosing melanoma in a human subject, as well as a method for providing a prognosis to a human subject who is at risk of developing melanoma recurrence, and a method for determining the stage of melanoma in a human subject, comprising the step of determining the level of expression of phosphatase and actin regulator 1 (PHACTR1) gene, or fragments thereof, either alone or in combination with the level of expression of secreted integrin-binding phosphoprotein (SPP1), preferentially expressed antigen in melanoma (PRAME), growth differentiation factor 15 (GDF15), and chemokine C-X-C motif ligand 10 (CXCL10) genes. Further, the invention relates to a diagnostic kit, comprising at least one substance for detection of the expression of PHACTR1, or fragments thereof, either alone or in combination with the detection of SPP1, PRAME, GDF15, and CXCL10, for the diagnosis or prognosis of melanoma.

A transgenic non-human aquatic organisms, such as piscine, crustacean, mollusks, and the like, having a transgene which results in disrupting the production of and / or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the aquatic organism is disclosed. Also disclosed are methods for making such organisms and nucleic acid sequences encoding GDF-8 polypeptides from such aquatic organisms.

Disclosed are novel methods for increasing muscle mass by means of immunization against Growth Differentiation Factor 8 (GDF-8, myostatin). Immunization is preferably effected by administration of analogues of GDF-8 which are capable of inducing antibody production against homologous GDF-8. Especially preferred as an immunogen is homologous GDF-8 which has been modified by introduction of one single or a few foreign, immunodominant and promiscuous T-cell epitopes while substantially preserving the tertiary structure of the homologous GDF-8. Also disclosed are nucleic acid vaccination against GDF-8 and vaccination using live vaccines as well as methods and means useful for the vaccination. Such methods and means include methods for identification of useful immunogenic GDF-8 analogues, methods for the preparation of analogues and pharmaceutical formulations, as well as nucleic acid fragments, vectors, transformed cells, polypeptides and pharmaceutical formulations.

A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and / or activity of growth differentiation factor-11 (GDF-11) chromosomally integrated into the germ cells of the animal is provided. Also provided are methods for making such animals, and methods of treating animals, including humans, with antibodies or antisense directed to GDF-11. The animals so treated are characterized by increased muscle tissue and bone tissue.

The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including GDF-8 (myostatin) receptor, and functional peptide portions thereof. Additionally, the present invention provides a virtual representation of the GDF receptor or a functional peptide portion thereof. The present invention also provides a method for modulating the cellular effects of myostatin by contacting the cells with a drug that affects myostatin signal transduction in the cells. In addition, the present invention provides a method of ameliorating a serious pathological condition at least partially characterized by an abnormal Characterized by weight, development or metabolic activity. The invention also provides a method of modulating the growth of muscle or adipose tissue in a eukaryotic organism by administering to the organism an agent that affects myostatin signal transduction.

Embodiments of the invention are related generally to the methods of diminishing the signs of aging in and / or improving health of human integuments, such as skin, and compositions comprising peptides useful therefor. The compositions according to the invention may comprise one or more peptides or fragments or derivatives thereof derived from a growth factor, e.g., Growth Differentiation Factor 11 (GDF11), in a topically acceptable vehicle.

The present invention relates to metformin for use in treating a patient, wherein the patient exhibits an increased level of GDF15 in response to metformin treatment; to methods of identifying a patient who will benefit or who will not benefit from metformin treatment; methods of treating a patient at risk of developing or suffering from a disease or disorder comprising administering therapeutically effective amount of metformin; methods of adapting the dosage of metformin; the usage of GDF15 as biomarker for identifying a patient who will benefit or who will not benefit from metformin treatment, kits for use in identifying a patient who will benefit from metformin treatment and the use of the kits, as well as methods of treating a patient or who will not benefit from metformin treatment.

The invention discloses a human growth differentiation factor-15 magnetic particle chemiluminescence detection kit and application thereof, the kit contains a liquid reagent R1 of a GDF15 monoclonal antibody 1 marked with FITC, a liquid reagent R2 of a GDF15 monoclonal antibody 2 marked with ALP, a magnetic particle reagent R3 coupled with an anti-FITC antibody, a calibration product and a quality control product, the GDF15 monoclonal antibody 1 and the GDF15 monoclonal antibody 2 are monoclonal antibodies with different antigen recognition epitopes, and the GDF15 monoclonal antibody 1 and the GDF15 monoclonal antibody 2 and a growth differentiation factor-15 can form a compound in an antibody-antigen-antibody form. The GDF15 is detected through a magnetic particle chemiluminescence method, the method is high in detection speed, high in sensitivity, large in detection flux and easy to operate in clinical detection, full-automatic operation can be achieved on a luminescence instrument, time and labor are saved, and convenience and rapidness are achieved.

The present invention relates to a method for inducing the differentiation of CD34+ hematopoietic stem cells into megakaryocytes and platelets, more particularly, a method for inducing the differentiation of CD34+ hematopoietic stem cells into megakaryocytes and platelets comprising the steps of coculturing CD34+ hematopoietic stem cells with stromal cells and adding the compound of Formula 1. Further, the present invention relates to a composition for detecting the differentiation of hematopoietic stem cells into megakaryocytes and platelets, comprising an agent measuring expression level of a gene that is selected from the group consisting of KLF2 (Kiruppel-like factor2), LOC138255 (OTTHUMP00000021439), GDF15 (growth differentiation factor 15) and INHBE (inhibin, betaE), a kit comprising the composition, a method for detecting the differentiation into megakaryocytes and platelets by using the marker genes, a method for regulating the differentiation into megakaryocytes and platelets, and a method for screening a candidate compound that regulates the differentiation into megakaryocytes and platelets.

The present invention discloses use of 15 genetic polymorphic sites of growth differentiation factor in predicting hypertensive secondary left ventricular hypertrophy, and belongs to the field of medical molecular biological technology. The present invention is superior in that it determines the action of GDF15 genetic polymorphism in hypertensive secondary left ventricular hypertrophy, and utilizes relevant SNP for providing medicine targets in treating hypertensive secondary left ventricular hypertrophy and providing guide in individualized diagnosis and prognosis.

The invention discloses a modified growth differentiation factor, which is formed by coupling a modified article and a growth differentiation factor, wherein the growth differentiation factor is (a) a natural growth differentiation factor 11 from a mammal; (b) protein or polypeptide which is obtained through performing replacement and / or deletion and / or addition on the amino acid sequence of the natural growth differentiation factor 11 by one or a plurality of amino acid residues, has nerve cell regeneration promotion capability and is derived from the natural growth differentiation factor 11; or (c) protein or polypeptide which has at least 50 percent of homology with the amino acid sequence shown by (a) or (b), has the nerve cell regeneration promotion capability and is derived from the amino acid sequence shown by (a) or (b). The modified growth differentiation factor provided by the invention can be better used for preventing, relieving and treating Alzheimer's diseases, and also achieves the effect of enhancing the memory. In addition, a metabolite regulated and controlled by the growth differentiation factor has the application of diagnosing and screening the Alzheimer's diseases.

The invention relates to application of growth differentiation factor 11 in the preparation of a medicine for treating ischemic stroke. In the rat model of focal cerebral ischemia reperfusion caused by middle cerebral artery occlusion, treatment and prevention effect of the growth differentiation factor (GDF11) on cerebral ischemic injury is researched. It is found that the GDF11 has functions ofreducing cortical ischemia volume and improving and recovering animal exercise capacity, and furthermore it is found that the GDF11 has a mechanism of action in treating and preventing cerebral ischemic injury and the process is realized by activating a Smad2 / 3 signal channel. The GDF11 can be designed as a targeted drug to prevent and treat ischemic stroke. The invention has latent huge application value for clinical prevention and treatment of ischemic stroke and lays a foundation for further research on biological function of the GDF11.

The present invention relates to a method for identifying a subject being eligible to the administration of at least one medicament selected from the group consisting of a beta blocker, an aldosterone antagonist, a diuretic, and an inhibitor of the renin-angiotensin system. The method is based on the determination of the amount of at least one biomarker selected from the group consisting of GDF-15 (Growth Differentiation Factor 15), endostatin, mimecan, IGFBP7 (IGF binding protein 7), a cardiac Troponin, a BNP-type peptide, uric acid, Gal3 (Galectin-3), osteopontin, sST2 (soluble ST2), PlGF, sFlt-1, P1NP, Cystatin C, Prealbumin, and Transferrin in a sample from a subject suffering from heart failure. Further, the method comprises the step of comparing the, thus, determined amount with a reference amount. Further envisaged by the present invention are kits and devices adapted to carry out the method of the present invention. The present invention also relates to a system for identifying a subject being eligible to the administration of at least one medicament as disclosed herein and to reagents and kits used in performing the methods as disclosed herein.