Abstract: A bioenvironment-sensitive nanoparticle including a polymer having complementary charges, a method of manufacturing the same, and a pharmaceutical use of the bioenvironment-sensitive nanoparticle are disclosed. The bioenvironment-sensitive nanoparticle can be useful in stably and effectively delivering a target material such as a drug even when used at a small quantity since the nanoparticle is stable in extracellular environments. Also, the bioenvironment-sensitive nanoparticle can be useful in selectively diagnosing or treating cancer cells since the nanoparticle is specific to environments of the cancer cells.

Abstract: Disclosed is an oral delivery system that overcomes major barriers encountered in the gastrointestinal tract, particularly rapid proteolytic degradation and low intestinal permeability. Provided is a method for oral delivery of an engineered microorganism to a mammal where the microorganism produces a macromolecule having a desired bioavailability outcome.

Abstract: A method of treating or preventing cognitive impairment deficits in subjects with age-associated cognitive decline or a dementing illness includes administering to the subject a therapeutically effective amount of amylin, an amylin agonist, or an amylin derivative to treat the cognitive impairment or deficit.

Abstract: An oral combination therapy or oral composition that protects orally administered exogenous leptin from the environment of the gastrointestinal tract, allowing delivery of the exogenous leptin to the bloodstream. The oral combination therapy includes (a) leptin or a leptin functional derivative; (b) a stomach acid-neutralizing agent such as a buffer; and (c) a pancreatic protease inhibitor that protects the exogenous leptin from degradation by pancreatic enzymes; and (d) a bile acid or a bile acid analog that facilitates absorption of the exogenous leptin. The oral combination therapy or oral composition may also include at least one agent that stimulates endogenous leptin secretion; as well as at least one agent capable of promoting, enhancing or improving adherence to treatment such as a sweetener or a satiety triggering agent.

Abstract: The present invention is directed to methods for modulating the Th/Th2 cell balance toward anti-inflammatory cytokine producing cells in a subject comprising decreasing the amount, the expression, or the activity of leptin in a subject sufficient to modulate the Th1/Th2 cell balance toward anti-inflammatory cytokine producing cells. The invention is also directed to methods of treatment of an immune-related disorder in a subject comprising decreasing the amount, the expression, or the activity of leptin in the subject sufficient to treat the immune-related disorder.

Abstract: Peptides are provided having leptin receptor agonist activity. The peptides are useful for treating obesity, type II diabetes, appetite control after bariatric surgery, insulin resistance, lipodystrophy and hypothalamic amenorrhea, obesity-related infertility, among other diseases and conditions related to leptin deficiency and/or leptin resistance.

Abstract: The present invention is directed to methods for modulating the Th1 /Th2 cell balance toward anti-inflammatory cytokine producing cells in a subject comprising decreasing the amount, the expression, or the activity of leptin in a subject sufficient to modulate the Th1 /Th2 cell balance toward anti-inflammatory cytokine producing cells. The invention is also directed to methods of treatment of an immune-related disorder in a subject comprising decreasing the amount, the expression, or the activity of leptin in the subject sufficient to treat the immune-related disorder.

Abstract: Leptin muteins, in particular leptin antagonists, with increased binding affinity to leptin receptor are provided. These compounds as well as pharmaceutical composition comprising them are useful for the treatment of any disorder in which a non-desirable or deleterious activity of endogenous leptin or an altered innate immune response is implicated.

Abstract: The present disclosure provides compositions containing a leptin product and methods of clinical therapy and diagnostic methods for progressive cognitive disorders. According to one aspect, the described invention provides a method for treating a progressive cognitive disorder. According to another aspect, the described invention provides a method for improving resilience of cognitive function in a subject in need thereof. According to another aspect, the described invention provides a method for identifying an effective therapeutic agent for treating a progressive cognitive dysfunction disease or disorder that results from at least one of accumulation of A?, hyperphosphorylation of tau, or accumulation of neurofibrillary tangles.

Abstract: Multifunctional polymers are disclosed having a smart segment and a biodegradable segment. Advantageously, the biodegradable segment includes a hydrophilic segment and a hydrophobic segment. Embodiments include combining the multifunctional polymeric material with a biologically active substance in an aqueous loading environment and administering the composition as a drug delivery vehicle to a human subject.

Abstract: The present invention relates to the therapeutic use of activators of the zinc finger protein GLI3 in diseases that are associated with reduced Hedgehog signaling in hepatocytes, in particular Polycystic ovary syndrome, Steatosis hepatis, Steatohepatit is and/or Adipositas. The invention further relates to methods of treating an individual with said activator, a pharmaceutical composition comprising said activator and the use of said activator as food supplement.

Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-1 receptor agonistic activity.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: The present invention is directed to compositions and methods of preparation of phospholipid gels.

Abstract: The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

Abstract: The invention provides compositions, methods, and kits for increasing transport of GDNF across the blood brain barrier while allowing its activity to remain substantially intact. The GDNF is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.

Abstract: The present disclosure provides compositions containing a leptin product and methods of clinical therapy and diagnostic methods for progressive cognitive disorders. According to one aspect, the described invention provides a method for treating a progressive cognitive disorder. According to another aspect, the described invention provides a method for improving resilience of cognitive function in a subject in need thereof. According to another aspect, the described invention provides a method for identifying an effective therapeutic agent for treating a progressive cognitive dysfunction disease or disorder that results from at least one of accumulation of A?, hyperphosphorylation of tau, or accumulation of neurofibrillary tangles.

Abstract: The described invention provides methods for treating or preventing progression of a progressive cognitive disease, disorder or condition, and methods for improving resilience of cognitive function in a subject in need thereof.

Abstract: The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

Abstract: The invention relates to a therapeutic device for the delivery of therapeutic agents, e.g. a peptide such as leuprolide, via the vagina to a female mammal. In some embodiments, the invention also relates to methods for the treatment of obesity and eating disorders, diabetes, multiple sclerosis (MS), endometriosis, uterine fibroids, polycystic ovarian disease, various cancers such as breast cancer, acne, hirsutism, microbial or fungal or viral infections such as bacterial vaginosis or AIDS/HIV, and chronic diseases using a disclosed vaginal device.

Abstract: The described invention relates to compositions and methods for rescuing neurons from Alzheimer's Disease related pathways triggered by lipid burden or metabolic insult.

Abstract: The described invention provides methods for treating or preventing progression of a progressive cognitive disease, disorder or condition, and methods for improving resilience of cognitive function in a subject in need thereof.

Abstract: The invention relates to Leptin derivatives, compositions and therapeutic use there-of.

Abstract: Multifunctional polymers are disclosed having a smart segment and a biodegradable segment. Advantageously, the biodegradable segment includes a hydrophilic segment and a hydrophobic segment. Embodiments include combining the multifunctional polymeric material with a biologically active substance in an aqueous loading environment and administering the composition as a drug delivery vehicle to a human subject.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: The expression of a mRNA encoding a putative 76 amino acid, secreted protein (“Enho1”) was found to negatively correlate with fasting triglyceride and cholesterol levels. A recombinant adenovirus was used to increase the expression of Enho1 mRNA in two mouse models of obesity, KK-Ay and Lepob/Lepob mice. Over-expression of Enho1 by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. In addition, transgenic mice strains were made that over express Enho1 protein. Additionally, the expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by ENHO1 adenoviral treatment in Lepob/Lepob mice.

Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-1 receptor agonistic activity.

Abstract: The expression of a mRNA encoding a putative 76 amino acid, secreted protein (“Enho1”) was found to negatively correlate with fasting triglyceride and cholesterol levels. A recombinant adenovirus was used to increase the expression of Enho1 mRNA in two mouse models of obesity, KK-Ay and Lepob/Lepob mice. Over-expression of Enho1 by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. In addition, transgenic mice strains were made that over express Enho1 protein. Additionally, the expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by ENHO1 adenoviral treatment in Lepob/Lepob mice.

Abstract: Site-specific modifications of proteins at their N-termini are provided. In particular, a chemical modification of proteins at their N-termini via a transamination reaction to form homogeneous adducts such as, the corresponding oxime derivatives is provided. Methods of making and using the adducts in radio-labelling, molecular imaging applications, and treatment of disorders such as cancer, Crohn's disease, arthritis, atherothrombosis and plaque rupture are also provided.

Abstract: The disclosure provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Abstract: The invention generally relates to the use of leptin in the treatment of a leptin-responsive disease or condition in a non-lipodystrophic subject. More particularly, the invention is directed to the use of leptin in the treatment of a fatty liver disease in a non-lipodystrophic subject with a relative leptin deficiency. The invention includes methods for the treatment of nonalcoholic steatohepatitis (NASH), alcoholic fatty liver disease (AFLD), and nonalcoholic fatty liver disease (NAFLD) in a non-lipodystrophic subject. The invention includes the treatment of conditions ranging from ectopic lipid accumulation (steatosis) to cirrhosis.

Abstract: Leptin, leptin analogs, and leptin derivatives are used to treat patients with lipoatrophy. Leptin is effective against conditions of lipoatrophy for both genetic and acquired forms of the disease. A therapeutically effective amount of leptin can be administered in a variety of ways, including subcutaneously and using gene therapy methods. Methods of the present invention contemplate administration of leptin, leptin analogs, and leptin derivatives to patients having a leptin level of approximately 4 ng/ml or less before treatment.

Abstract: A method of treating or preventing cognitive impairment deficits in subjects with age-associated cognitive decline or a dementing illness includes administering to the subject a therapeutically effective amount of amylin, an amylin agonist, or an amylin derivative to treat the cognitive impairment or deficit.

Abstract: The described invention relates to methods for treating, preventing, or diagnosing the pathology of progressive cognitive disorders resulting from accumulation of an amyloid peptide, in particular, Alzheimer's disease, Down's syndrome and cerebral amyloid angiopathy, in mammalian subjects using a composition comprising therapeutically effective amount of a leptin, leptin mimic, leptin derivative, leptin agonist, or AMP-dependent protein kinase activator, alone, or in combination with, one or more lipolytic/antilipogenic compounds. It further relates to methods for improving cognitive function using a composition comprising a therapeutically effective amount of leptin, a leptin mimic, a leptin derivative, an AMP-dependent protein kinase activator, a leptin agonist, a leptin blocker, a mimic of a leptin blocker, a leptin antagonist, an AMP-dependent protein kinase inhibitor; or a pharmaceutically acceptable salt thereof.

Abstract: Peptides are provided having leptin receptor agonist activity. The peptides are useful for treating obesity, insulin resistance, lipodystrophy and hypothalamic amenorrhea, anorexia-related infertility, among other diseases and conditions related to leptin deficiency and/or leptin resistance.

Abstract: Leptin muteins, in particular leptin antagonists, with increased binding affinity to leptin receptor are provided. These compounds as well as pharmaceutical composition comprising them are useful for the treatment of any disorder in which a non-desirable or deleterious activity of endogenous leptin or an altered innate immune response is implicated.

Abstract: The described invention provides methods and compositions for enhancing the enzymatic activity of Sirtuin family members by using Leptin, Leptin analogs, Leptin derivatives, or Leptin agonists. The described invention further provides compositions and methods for delaying senescence or cell death in neurons using the compositions.

Abstract: Methods for treating obesity or obesity related disorders are disclosed. These methods include the use of anti-obesity agents directed to the forebrain in combination with anti-obesity agents directed to the hindbrain.

Abstract: Activators of the AKT/mTOR pathway, in particular leptin, are useful in methods and compositions for increasing regeneration of liver, increasing liver mass or improving liver function, or a combination thereof.

Abstract: Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

Abstract: Leptin, leptin analogs, and leptin derivatives are used to treat patients with lipoatrophy. Leptin is effective against conditions of lipoatrophy for both genetic and acquired forms of the disease. A therapeutically effective amount of leptin can be administered in a variety of ways, including subcutaneously and using gene therapy methods. Methods of the present invention contemplate administration of leptin, leptin analogs, and leptin derivatives to patients having a leptin level of approximately 4 ng/ml or less before treatment.

Abstract: The present invention relates to methods for treating, preventing, or diagnosing the pathology of progressive cognitive disorders resulting from accumulation of an amyloid peptide, in particular, Alzheimer's disease, Down's syndrome and cerebral amyloid angiopathy, in mammalian subjects using a composition comprising therapeutically effective amount of a leptin, leptin mimic, leptin derivative, leptin agonist, or AMP-dependent protein kinase activator, alone, or in combination with, one or more lipolytic/antilipogenic compounds. It further relates to methods for improving cognitive function using a composition comprising a therapeutically effective amount of leptin, a leptin mimic, a leptin derivative, an AMP-dependent protein kinase activator, a leptin agonist, a leptin blocker, a mimic of a leptin blocker, a leptin antagonist, an AMP-dependent protein kinase inhibitor; or a pharmaceutically acceptable salt thereof.

Abstract: A formulation of a diluted amino acid segment is prepared by mixing an amino acid segment and a diluting agent to form a mixture. The mixture is serially diluted to produce a diluted formulation. The amino acid segment includes a peptide sequence that is the same as a portion of a longer peptide sequence found in a naturally occurring material. A homeopathic remedy can be prepared using the formulation.

Abstract: The present invention relates to novel compounds having a function of a peptide in the amylin family, related nucleic acids, expression constructs, host cells, and processes production of the compounds. The compounds of the invention include one or more amino acid sequence modifications. In addition, methods and compositions are disclosed to treat and prevent metabolic disorders such as obesity, diabetes, and increased cardiovascular risk.

Abstract: The present invention relates to methods for treating, preventing, or diagnosing the pathology of progressive cognitive disorders resulting from accumulation of an amyloid peptide, in particular, Alzheimer's disease, Down's syndrome and cerebral amyloid angiopathy, in mammalian subjects using a composition comprising therapeutically effective amount of a leptin, leptin mimic, leptin derivative, leptin agonist, or AMP-dependent protein kinase activator, alone, or in combination with, one or more lipolytic/antilipogenic compounds. It further relates to methods for improving cognitive function using a composition comprising a therapeutically effective amount of leptin, a leptin mimic, a leptin derivative, an AMP-dependent protein kinase activator, a leptin agonist, a leptin blocker, a mimic of a leptin blocker, a leptin antagonist, an AMP-dependent protein kinase inhibitor; or a pharmaceutically acceptable salt thereof.

Abstract: Modified human leptin polypeptides and uses thereof are provided.

Abstract: The present invention provides for methods of treating type I diabetes by inducing hyperleptinemia in subjects afflicted with type I diabetes. These methods can achieve normoglycemia and suppress hypergluconemia, and alleviate conditions associated with such, even in the absence of or at extremely low levels of adjunct insulin therapy, and without any appreciable increase in insulinogenesis.

Abstract: Novel MCH-1 receptor antagonists are disclosed. These compounds are used in the treatment of various disorders, including obesity, anxiety, depression, non-alcoholic fatty liver disease, and psychiatric disorders. Methods of making these compounds are also described in the present invention.

Abstract: Novel MCH-1 receptor antagonists are disclosed. These compounds are used in the treatment of various disorders, including obesity, anxiety, depression, non-alcoholic fatty liver disease, and psychiatric disorders. Methods of making these compounds are also described in the present invention.

Abstract: Novel MCH-1 receptor antagonists are disclosed. These compounds are used in the treatment of various disorders, including obesity, anxiety, depression, non-alcoholic fatty liver disease, and psychiatric disorders. Methods of making these compounds are also described in the present invention.