The present invention relates to the identification of a microRNA family, designated miR-29a-c, that is a key regulator of fibrosis in cardiac tissue. The inventors show that members of the miR-29 family are down-regulated in the heart tissue in response to stress, and are up-regulated in heart tissue of mice that are resistant to both stress and fibrosis. Also provided are methods of modulating expression and activity of the miR-29 family of miRNAs as a treatment for fibrotic disease, including cardiac hypertrophy, skeletal muscle fibrosis other fibrosis related diseases and collagen loss-related disease.

The present invention relates to a secretin receptor modulator for use in the prevention and/or treatment of a disease or disorder of energy homeostasis, wherein (a) said secretin receptor modulator is a secretin receptor agonist and said disease or disorder is obesity, dyslipidemia, diabetes, insulin resistance, hyperglycemia, high blood pressure or metabolic syndrome, whereby the secretin receptor agonist increases non-shivering thermogenesis in brown adipocytes and/or increases the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or decreases food intake in a UCP1-dependent manner resulting in the prevention and/or treatment of said disease or disorder; or (b) said secretin receptor modulator is a secretin receptor antagonist and said disease or disorder is cachexia. The invention further relates to a method of increasing non-shivering thermogenesis in brown adipocytes and/or increasing the expression of uncoupling protein 1 (UCP1) in brown adipocytes, to a method of decreasing non-shivering thermogenesis in brown adipocytes, to a method of identifying a secretin receptor agonist capable of increasing non-shivering thermogenesis in brown adipocytes and/or increasing the expression of uncoupling protein 1 (UCP1) in brown adipocytes, to a method of identifying a secretin receptor antagonist capable of decreasing non-shivering thermogenesis in brown adipocytes, to the use of the secretin receptor for screening (a) for secretin receptor agonists that increase non-shivering thermogenesis in brown adipocytes and/or increase the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or decrease food intake in a UCP1-dependent manner; and/or (b) for secretin receptor antagonists that decrease non-shivering thermogenesis in brown adipocytes, and to the use of a secretin receptor agonist to activate non-shivering thermogenesis in brown adipocytes and/or to increase the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or to decrease food intake in a UCP1-dependent manner for reducing body weight for cosmetic purposes as well as to the use of a secretin receptor antagonist to decrease thermogenesis in brown adipocytes for increasing body weight for cosmetic purposes.

The present invention relates to a secretin receptor modulator for use in the prevention and/or treatment of a disease or disorder of energy homeostasis, wherein (a) said secretin receptor modulator is a secretin receptor agonist and said disease or disorder is obesity, dyslipidemia, diabetes, insulin resistance, hyperglycemia, high blood pressure or metabolic syndrome, whereby the secretin receptor agonist increases non-shivering thermogenesis in brown adipocytes and/or increases the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or decreases food intake in a UCP1-dependent manner resulting in the prevention and/or treatment of said disease or disorder; or (b) said secretin receptor modulator is a secretin receptor antagonist and said disease or disorder is cachexia. The invention further relates to a method of increasing non-shivering thermogenesis in brown adipocytes and/or increasing the expression of uncoupling protein 1 (UCP1) in brown adipocytes, to a method of decreasing non-shivering thermogenesis in brown adipocytes, to a method of identifying a secretin receptor agonist capable of increasing non-shivering thermogenesis in brown adipocytes and/or increasing the expression of uncoupling protein 1 (UCP1) in brown adipocytes, to a method of identifying a secretin receptor antagonist capable of decreasing non-shivering thermogenesis in brown adipocytes, to the use of the secretin receptor for screening (a) for secretin receptor agonists that increase non-shivering thermogenesis in brown adipocytes and/or increase the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or decrease food intake in a UCP1-dependent manner; and/or (b) for secretin receptor antagonists that decrease non-shivering thermogenesis in brown adipocytes, and to the use of a secretin receptor agonist to activate non-shivering thermogenesis in brown adipocytes and/or to increase the expression of uncoupling protein 1 (UCP1) in brown adipocytes and/or to decrease food intake in a UCP1-dependent manner for reducing body weight for cosmetic purposes as well as to the use of a secretin receptor antagonist to decrease thermogenesis in brown adipocytes for increasing body weight for cosmetic purposes.

The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.

Disclosed is a protein aqueous suspension preparation containing a protein and a polyamino acid, the protein and the polyamino acid having a surface charge in a buffer and forming a complex suspended in the buffer, wherein the absolute value of the difference between pH of the buffer and isoelectric point pI of the protein is in the range of from 0.5 to 4.0. Also disclosed are a method of preparing a protein aqueous suspension preparation and a prefilled syringe containing a concentrated protein aqueous suspension preparation. The protein can exhibit at least one of shaking stress resistance, fluidity enhancement, oxidation resistance, thermal stability, and aggregation inhibitory properties.

This disclosure relates to a drug delivery system comprising an intraocular pressure lowering agent, a neurotrophic agent, such as a CNTF compound, a C-type Natriuretic Peptide (CNP) compound, a Tie-2 agonist, a Natriuretic Peptide Receptor-B (NPR-B) compound, or an apoptosis signaling fragment inhibitor (FAS) or FAS-ligand (FASL) inhibitor, including any combination of these compounds and a sustained delivery component. Methods of treating a glaucoma or related conditions, medicaments, kits, uses and methods of manufacturing are also described.

This disclosure relates to a drug delivery system comprising an intraocular pressure lowering agent, a neurotrophic agent, such as a CNTF compound, a C-type Natriuretic Peptide (CNP) compound, a Tie-2 agonist, a Natriuretic Peptide Receptor-B (NPR-B) compound, or an apoptosis signaling fragment inhibitor (FAS) or FAS-ligand (FASL) inhibitor, including any combination of these compounds and a sustained delivery component. Methods of treating a glaucoma or related conditions, medicaments, kits, uses and methods of manufacturing are also described.

Methods of treating a subject having heart failure including heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, and left ventricular hypertrophy-induced heart failure. The methods include activating hypothalamic oxytocin neurons in the brain of the subject and/or administering intranasally to the subject a therapeutically effective amount of oxytocin. Intranasal formulations for the treatment of a subject diagnosed with heart failure are also provided.

Methods of treating a subject having heart failure including heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, and left ventricular hypertrophy-induced heart failure. The methods include activating hypothalamic oxytocin neurons in the brain of the subject and/or administering intranasally to the subject a therapeutically effective amount of oxytocin. Intranasal formulations for the treatment of a subject diagnosed with heart failure are also provided.

The present invention provides a therapeutic agent for failure-to-thrive or short stature which contains C-type natriuretic peptide (CNP) or a CNP derivative as an active ingredient, reduces adverse reactions, and exhibits excellent efficacy, and a method for treating failure-to-thrive or short stature.