Abstract: The object of the invention is to provide a pharmaceutical composition of a hydrophobically modified hedgehog protein containing a biocompatible carrier, wherein the carrier binds the hedgehog protein as an active folded structure and can release it locally in vivo in an active form in a delayed manner. Such formulations are particularly suitable for the repair of bone and cartilage defects and can also be used to repair neuronal defects or for a systemic delivery. The object is achieved by a pharmaceutical composition of a hydrophobically modified hedgehog protein which is characterised in that this composition contains hydrophobically modified hedgehog proteins and a biodegrable protein or a proteolytic degradation product thereof as a carrier.

Abstract: Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.

Abstract: The invention is a treatment for increasing the bone mass or preventing bone loss in an individual afflicted with a bone disease which includes administering to the individual a morphogen in a therapeutically effective amount so as to maintain or stimulate bone formation.

Abstract: The present invention makes available an optimal concentration of a hedgehog polypeptide for modulating growth and/or cartilage production by chondrocytes. The present invention allows for improvements in the culturing of chondrocytes to develop cartilaginous tissue ex vivo suitable for implantation to replace damaged or deteriorated cartilage in a patient.

Abstract: The present invention provides isolated highly active hedgehog proteins esterified with a fatty acid having from 14 to 20 carbon atoms at the N-terminal domain of the protein. The highly active hh proteins are particularly useful therapeutic agents for treating bone disorders and neurodegenerative diseases. Methods for obtaining the highly active modified hedgehog proteins are also provided.

Abstract: The present invention provides isolated highly active hedgehog proteins esterified with a fatty acid having from 14 to 20 carbon atoms at the N-terminal domain of the protein. The highly active hh proteins are particularly useful therapeutic agents for treating bone disorders and neurodegenerative diseases. Methods for obtaining the highly active modified hedgehog proteins are also provided.

Abstract: Disclosed are methods and compositions for maintaining neural pathways in a mammal including: enhancing survival of neurons at risk of dying; inducing cellular repair of damaged neurons and neural pathways; stimulating neurons to maintain their differentiated phenotype; and promoting dendritic outgrowth, including maintaining dendritic arbors and regenerating dendritic architecture. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule in an amount sufficient to control the aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. The present invention further makes available methods and reagents for ameliorating the consequences of hedgehog loss-of-function, ptc gain-of-function, or smoothened loss-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule, in an amount sufficient to ameliorate the In certain embodiments, the subject compounds, e.g., a cAMP analog, adenylate cyclase agonist, or cAMP phosphodiesterase inhibitor, regulate cAMP levels, which in turn modulates activity of the hedgehog pathway.

Abstract: The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. The invention provides a method to promote T lymphocyte development using low dose Hedghog, and a method to inhibit T lumphocyte development using high dose Hedgehog. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.

Abstract: The instant application relates to methods and reagents for modulating the Hedgehog signaling pathway using RNA interference technology (RNAi). The application provides potential targets of the Hedgehog RNAi, methods to identify additional Hedgehog signaling pathway components, methods to inhibit Hedgehog signaling targets using siRNA, and their uses in the treatment of a number of disease conditions.

Abstract: Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularly OP-1-binding cell surface receptors; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

Abstract: The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.

Abstract: Disclosed are methods and compositions for maintaining neural pathways in a mammal including: enhancing survival of neurons at risk of dying; inducing cellular repair of damaged neurons and neural pathways; stimulating neurons to maintain their differentiated phenotype; and promoting dendritic outgrowth, including maintaining dendritic arbors and regenerating dendritic architecture. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

Abstract: Disclosed are methods and compositions for identifying compounds having an ability to modulate expression of a morphogen, particularly OP-1, OP-1 homologues and closely related proteins, using one or more OP-1-specific, non-coding sequences and a suitable reporter gene. In preferred embodiments, the OP-1-specific non-coding DNA sequence comprises a Pax-responsive OP-1-modulating element.

Abstract: The present invention concerns the methods and compositions for treating depression and other behavioral and/or emotional disorders of the central nervous system by administering an agonist of hedgehog signaling. Other disorders amenable to treatment by the subject method include attention deficit hyperactive disorders, non-Alzheimer dementia, and various symptoms of memory loss. The present invention also concerns the methods and compositions for enhancing memory and/or cognitive functions, both in a patient suffering from ailment affecting these functions, and in a subject with no diagnosed deficit in memory or cognitive function. The methods and compositions of the present invention stimulate neurogenesis and differentiation, and enhance synaptic transmission of neurons.

Abstract: OP/BMP morphogen is combined with GDNF/NGF neurotrophic factors in promoting the survival or growth, or inhibiting the death or degeneration, of mammalian cells, particularly neural cells, which express OP/BMP-activated serine/threonine kinase receptors and GDNF/NGF-activated tyrosine kinase receptors. Also discosed are methods for the treatment of such cells, including treatments for mammals afflicted with, or at imminent risk of, damage or injury to, such cells, as well as new pharmaceutical preparations for such treatments.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain proteins of, or based upon, the osteogenic protein/bone morphogenetic protein (OP/BMP) family within the TGF-? superfamily of proteins.

Abstract: Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Abstract: Anti-hedgehog antibodies directed at blocking the binding of hedgehog to its receptor patched-1, will impair lipid metabolism and storage. This invention presents methods for the treatment of a variety of lipid metabolism and lipid storage disorders, aberrant apolipoprotein expression, atherosclerosis and other lipid associated disorders using lipid modulators such as hedgehog antagonists or hedgehog agonists.