Abstract: Insulin-like growth factor-binding protein 3 receptor (IGFBP-3R) agonists and methods of their use to treat diseases involving IGFBP-3 and IGFBP-3R are provided. The agonists may be antibodies or other molecules specific for binding to and activating IGFBP-3R. The agonists are used to treat e.g. cancer, metabolic syndrome and obstructive respiratory disorders. In addition, methods of diagnosing cancer and predicting the chance of recurrence, metastasis and/or survival by measuring the level of IGFBP-3R in tumor tissue are provided.

Abstract: The invention relates to methods of using an effective amount of activated protein C (APC) to treat an individual for a skin disorder characterised by the presence of hyperproliferative keratinocytes.

Abstract: The present invention relates to a method for PEGylating interferon beta.

Abstract: This invention concerns pathological angiogenesis and cancer, related treatment methods, and related compositions. Also disclosed are related diagnosis kits and methods.

Abstract: A method is provided for treating a disease or condition characterized by aberrant epithelial cell proliferation and/or migration. One step of the method can include administering to a mammal an agent which disrupts an isolated protein complex including: insulin-like growth factor I (IGF-I); an insulin-like growth factor binding protein (IGFBP) selected from IGFBP-3 and IGFBP-5; and vitronectin; or which prevents formation of the isolated protein complex, to thereby treat the disease or condition in the mammal. The agent is selected from the group consisting a polypeptide that is distinguished from IGF-II by substitution of at least one amino acid residue, wherein the polypeptide disrupts the isolated protein complex.

Abstract: Provided are methods of regulating keratinocytes proliferation and differentiation by subjecting keratinocytes to an agent capable of modulating activity or expression of IGFBP7, thereby regulating keratinocytes proliferation and differentiation. Also provided are methods of treating pathologies characterized by hyperproliferative keratinocytes by administering IGFBP7 polypeptide or a polynucleotide encoding IGFBP7 polypeptide to a subject.

Abstract: Disclosed herein are compounds, compositions and methods for treatment of diseases and disorders, including spinal muscular atrophy.

Abstract: Compositions comprising IGFBP-3 receptor agonists and methods for the treatment of metabolic syndrome, obstructive respiratory disorders, obstructive or inflammatory respiratory disease, cancers and related diseases with IGFBP-3 receptor agonists are presented. A method for interfering with the activity of nuclear factor-kappaB (NF-KB) in a cell, comprising: providing to a cell an effective amount of a composition comprising an IGFBP-3 receptor agonist; and interfering with the activity of NF-KB in the cell is included.

Abstract: Methods of treating a tumor in a subject include identifying a subject having, at risk for, or suspected of having a tumor, and administering to the subject an effective amount of an IGFBP7 agent if the tumor has increased Ras-BRAF-MEK-Erk signaling, is dependent for growth and/or survival upon the Ras-BRAF-MEK-Erk signaling pathway, and/or expresses an activated or oncogenic BRAF or RAS.

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: Disclosed is a method of promoting neuronal growth by administering IGFBPL-1, or an agent that increases or stabilizes IGFBPL-1 activity to a subject in need thereof, e.g., a subject in need of treating optic nerve degeneration.

Abstract: The present invention relates to a pharmaceutical composition for inhibiting angiogenesis comprising an isolated peptide comprising the heparin-binding domain of insulin-like growth factor-binding protein-5 (IGFBP-5), a method for inhibiting angiogenesis using the peptide, a pharmaceutical composition for the prevention or treatment of cancer comprising the peptide, a method for treating cancer using the peptide, a novel angiogenesis-inhibiting peptide derived from heparin-binding domain of IGFBP-5, a polynucleotide encoding the peptide, an expression vector comprising the polynucleotide and a transformant comprising the vector.

Abstract: Formulations of cross-linkable polymers, capable of forming non-toxic and biocompatible hydrogels in situ, containing at least one of doxycycline or minocycline. Methods of using the hydrogels for treating the skin or ocular tissues of mammals exposed to vesicant compounds such as sulfur mustard (SM), nitrogen mustard (NM) or half mustard (2-chloroethyl ethyl sulfide (CEES)) are also disclosed.

Abstract: A method is provided for treating a disease or condition characterized by aberrant epithelial cell proliferation and/or migration. One step of the method can include administering to a mammal an agent which disrupts an isolated protein complex including: insulin-like growth factor I (IGF-I); an insulin-like growth factor binding protein (IGFBP) selected from IGFBP-3 and IGFBP-5; and vitronectin; or which prevents formation of the isolated protein complex, to thereby treat the disease or condition in the mammal. The agent is selected from the group consisting a polypeptide that is distinguished from IGF-II by substitution of at least one amino acid residue, wherein the polypeptide disrupts the isolated protein complex.

Abstract: The present invention provides polypeptide derivatives of IGFBP-3 that are resistant to proteolytic cleavage. These IGFBP-3 derivatives are useful in a variety of therapeutic and diagnostic applications. Also provided are pharmaceutical compositions and kits comprising such IGFBP-3 derivatives and methods for using these derivatives for the treatment of a variety of disorders.

Abstract: The present invention provides innovative proteins that bind to insulin-like growth factor-I receptor (IGF-IR), as well as other important proteins. The invention also provides innovative proteins in pharmaceutical preparations and derivatives of such proteins and the uses of same in diagnostic, research and therapeutic applications. The invention further provides cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins.

Abstract: An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.

Abstract: The present invention is directed to methods of treating Type 1-diabetes by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods treating Type 2 diabetes by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is further directed to methods treating insulin resistance by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is directed to methods of treating hepatic steatosis by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods lowering blood glucose and serum insulin in non-diabetic subjects by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2.

Abstract: The present invention relates to a composition comprising Insulin Growth Factor I (IGF-I) or an analog thereof in combination with Insulin Growth Factor Binding Protein (IGFBP) or an analog thereof, such combination having a molar ratio of IGF-I to IGFBP being lower than equimolar, preferably in the range from 1:20 to 1:3.33, for use in the treatment of a patient suffering from complications of preterm birth, very preterm birth and/or extremely preterm birth, as well as a method for treating a patient suffering from complications of preterm birth, very preterm birth and/or extremely preterm birth.

Abstract: The present invention is directed to methods of treating Type 1-diabetes by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods treating Type 2 diabetes by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is further directed to methods treating insulin resistance by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is directed to methods of treating hepatic steatosis by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods lowering blood glucose and serum insulin in non-diabetic subjects by administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2.

Abstract: This invention relates to methods of inducing differential stress resistance in a subject with cancer by starving the subject for a short term, administering a cell growth inhibitor to the subject, or reducing the caloric or glucose intake by the subject. The induced differential stress resistance results in improved resistance to cytotoxicity in normal cells, which, in turn, reduces cytotoxic side-effects due to chemotherapy, as well as improved effectiveness of chemotherapeutic agents.

Abstract: The present invention provides a method treating a myeloma patient by administering one or more of thalidomide, a Total Therapy 2 regimen, an interleukin-6 signaling suppressor, an interleukin-6R signaling suppressor, an IGF1 signaling suppressor, an IGF1 R signaling suppressor, shRNA or other modulators of gene expression. Also, provided are methods for predicting outcome of a treatment for an individual having a cancer, e.g., myeloma, by performing one or more of karyotyping or expression profiling of chromosomes 1 and 13 or expression level measurement of IL-6R.

Abstract: The invention relates to pharmaceutical compositions comprising trophic factors, methods to decrease the degeneration of a retina, methods of treating ocular degenerative diseases and methods to select cells for transplantation.

Abstract: The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of either an anti-IGF-1R antibody or an IGF binding protein (e.g. IGFBP3), and a small molecule IGF-1R kinase inhibitor (e.g. OSI-906). The present invention also provides a pharmaceutical composition comprising either an anti-IGF-1R antibody or an IGF binding protein (e.g. IGFBP3), and a small molecule IGF-1R kinase inhibitor (e.g. OSI-906), with a pharmaceutically acceptable carrier.

Abstract: The present invention provides methods and compositions for tissue regeneration without cell transplantation.

Abstract: A nutritional Composition for a subject, comprising prolactin identical or similar or analogous to prolactin found in a natural food source, and at least one protective layer, wherein release of said prolactin from the composition in said subject is the result of an environmental event.

Abstract: The invention discloses a bone implant and a manufacturing method thereof. The manufacturing method of the bone implant comprises a step of coating or mixing type II collagen with at least one porous bone material comprising metals, bio-ceramics, natural biopolymers and synthetic polymers. Another manufacturing method of the bone implant comprises the steps of loading type II collagen with or without at least one porous bone material in a container, and lyophilizing the type II collagen to generate a type II collagen sponge construct with or without the porous bone material as the bone material. The manufactured bone implants are effective, with or without loading cells having differentiation tendency towards osteogenesis, to facilitate bone repair upon introduction of the bone implant into various osseous defects.

Abstract: An injectable, high potency (high capillary force) composite comprised of bioceramic spheres having a smooth porous macroarchitecture and porous microarchitecture with interconnected pores and may be combined with various electrospun polymer fibers, thus achieving a biphasic composite implant device whereby a primary phase stabilizes, reinforces, restricts and constricts the expansion of dysfunctional and diseased cardiac muscle tissue, and a secondary phase providing a matrix structure within the bioceramic composite for the regeneration of dysfunctional and diseased cardiac tissue; an injectable composite implant material containing pharmaceutical agents or may contain stem cells, and other DNA materials; an injectable, high potency, bioceramic composite material providing a specific means to alter cardiac muscle geometry so as to normalize cardiac wall stress, aid in the reduction of local stresses in the border zone or in the actual infarct as well as multiple peri-infarct border zone modifications that h

Abstract: The present invention is directed to methods of treating Type I diabetes by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods treating Type 2 diabetes comprising the step of administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is further directed to methods treating insulin resistance comprising the step of administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2. The present invention is directed to methods of treating hepatic steatosis by administering a therapeutically effective amount of an Insulin-like Growth Factor-binding protein-2. The present invention is also directed to methods lowering blood glucose and serum insulin in non-diabetic subjects comprising the step of administering a therapeutically effective amount of Insulin-like Growth Factor-binding protein-2.

Abstract: Provided is a novel soluble factor that modulates morphogenesis and cell proliferation, such as cardiac development and/or cardiomyocyte differentiation. Specifically provided are: an inhibitor of Wnt signalling, comprising an insulin-like growth-factor-binding protein (IGFBP), the protein being binding to a Wnt receptor, and/or a polynucleotide encoding the protein; a medicament for prevention and/or treatment of a disease due to enhanced Wnt signalling, comprising the inhibitor of Wnt signalling, and a medicament for induction of cardiomyocyte differentiation; and a method for prevention and/or treatment of a disease due to enhanced Wnt signalling and a method of inducing cardiomyocyte differentiation, the methods each comprising using the inhibitor of Wnt signalling, and a cardiomyocyte, which is obtained by the method of inducing cardiomyocyte differentiation, and a use thereof.

Abstract: A method of enhancing eyelash and eye brow hair growth utilizes insulin and/or IFG-1 alone or in combination with other known hair growth promoting therapeutic, pharmaceutical, biochemical and biological agents to increase the effect of various therapeutic hair regrowth strategies to enhance eyelash and eye brow hair growth.

Abstract: Provided are methods of regulating keratinocytes proliferation and differentiation by subjecting keratinocytes to an agent capable of modulating activity or expression of IGFBP7, thereby regulating keratinocytes proliferation and differentiation. Also provided are methods of treating pathologies characterized by hyperproliferative keratinocytes by administering IGFBP7 polypeptide or a polynucleotide encoding IGFBP7 polypeptide to a subject.

Abstract: Complexes of IGF-I and IGFBP-3 with new levels of purity are provided. Chromatographic techniques have been developed that remove contaminants, such as mass and charge variants of IGFBP-3. The new techniques enable the production of high-quality pharmaceutical compositions comprising IGF-I/IGFBP-3 complexes.

Abstract: Embodiments of this invention provide methods for therapeutic use of cyclic G-2-allylProline (cG-2-allylP) to treat peripheral neuropathies, including toxin-induced peripheral neuropathy and diabetic as well as manufacture of medicaments including tablets, capsules, and other orally active compositions containing cG-2-allylP, as well as injectable solutions that are useful for treatment of such conditions.

Abstract: Embodiments of this invention provide novel peptidomimetics that contain a macrocycle. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterised by neuronal degeneration and/or death. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.

Abstract: The present invention provides methods and compositions for sequentially and separately reducing infection and/or inflammation and regenerating tissue at a lesion site, by contacting the lesion site with a biodegradable scaffold that first delivers one or more agents at the lesion site to reduce infection and/or inflammation and then delivers one or more agents to regenerate tissue at the lesion site after inflammation is reduced.

Abstract: The present invention provides a method of increasing neural stem cell numbers or neurogenesis by using prolactin. The method can be practiced in vivo to obtain more neural stem cells in situ, which can in turn produce more neurons or glial cells to compensate for lost or dysfunctional neural cells. The method can also be practiced in vitro to produce a large number of neural stem cells in culture. The cultured stem cells can be used, for example, for transplantation treatment of patients or animals suffering from neurodegenerative diseases or conditions. In addition, since neural stem cells are a source for olfactory neurons, the present invention also provides methods of increasing olfactory neurons and enhancing olfactory functions.

Abstract: The present invention relates to the use of proteins comprising at least one follistatin domain to modulate the level or activity of growth and differentiation factor-8 (GDF-8). More particularly, the invention relates to the use of proteins comprising at least one follistatin domain, excluding follistatin itself, for treating disorders that are related to modulation of the level or activity of GDF-8. The invention is useful for treating muscular diseases and disorders, particularly those in which an increase in muscle tissue would be therapeutically beneficial. The invention is also useful for treating diseases and disorders related to metabolism, adipose tissue, and bone degeneration.

Abstract: An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.

Abstract: The invention relates to the use of cyclic Prolyl Glycine (“cyclic PG” or “cPG”) and analogs and mimetic s thereof, as neuroprotective agents for the treatment and or prevention of neurological disorders including but not limited to cerebral ischemia or cerebral infarction resulting from a range of phenomena, such as thromboembolic or hemorrhagic stroke, cerebral basospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery, and cerebral trauma, as well as to the treatment and prevention of chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, and as anticonvulsants.