Abstract: The present invention generally relates to the field of treatment of neuronal disorders and more particularly to neurotrophic factor MANF and uses thereof. The present invention provides a pharmaceutical compound comprising MANF nucleic acid molecule, MANF protein or a functional fragment thereof for the treatment of a peripherial neuropathy including Alzheimer's disease, Parkinson's disease, epilepsy, drug addiction and ischemic brain injury.

Abstract: The present invention relates to the fields of knockout (KO) animal production. The invention is directed to a transgenic KO animal comprising a heterozygous or homozygous deletion or functional deletion of the gene's native 3? untranslated region (3?UTR) at least in one of its endogenous gene loci, wherein the disrupted endogenous gene is transcribed into an m RNA without its native 3?UTR. Instead, a 3?UTR of choice, knocked in by the experimenter, is transcribed into an m RNA. The 3?UTR KO animals provide a new approach to study gene function as they enable to overexpress the gene products what are negatively regulated via their 3?UTR-s exclusively in those cells that already transcribe the gene, thereby avoiding the misexpression problem present in the animals produced by conventional transgenesis methods. The invention is further directed to KO animals, in which the gene with deletion of 3?UTR is GDNF, NGF or BDNF.

Abstract: Neurturin polypeptides which possess reduced heparin and heparan sulfate binding affinity but retain neurotrophic activity, nucleic acids which encode the neurturin variants and vectors and host cells which express the enhanced neurturin polypeptides. Use of the enhanced neurturin polypeptides, nucleic acids and host cells in the treatment or prevention of disease.

Abstract: Neurturin polypeptides which possess reduced heparin and heparan sulfate binding affinity but retain neurotrophic activity, nucleic acids which encode the neurturin variants and vectors and host cells which express the enhanced neurturin polypeptides. Use of the enhanced neurturin polypeptides, nucleic acids and host cells in the treatment or prevention of disease.

Abstract: Disclosed are compounds and methods for treating neurological and other disorders by administering to a subject in need thereof an effective amount of a compound having binding and/or modulation specificity for GFR? receptor molecules, which can be mimetics of glial-derived neurotrophic factor (GDNF) family ligands (GFLs), GFR?/RET signaling pathway agonists, and/or direct RET agonists (activators).

Abstract: The present invention provides compounds having a chelating moiety and an oligonucleotide sequence wherein the oligonucleotide includes one or more modified nucleobases, such as hydroxynucleobases. The disclosed compounds are suitable for antisense therapy. The chelating moiety can be complexed to an ion of a lanthanide metal. These compounds are efficient translation inhibitors of nucleic acids and have increased binding affinity for target nucleic acids. The invention also includes compositions and methods of using these compositions as antisense therapy.

Abstract: Neurturin polypeptides which possess reduced heparin and heparan sulfate binding affinity but retain neurotrophic activity, nucleic acids which encode the neurturin variants and vectors and host cells which express the enhanced neurturin polypeptides. Use of the enhanced neurturin polypeptides, nucleic acids and host cells in the treatment or prevention of disease.

Abstract: A method for treating a condition in a patient, wherein the condition is selected from the group consisting of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and peripheral neuropathy. The method consists of administering to the patient a pharmaceutically effective amount of a pharmaceutical composition comprising the MANF2 polypeptide of SEQ ID NO:2 or a functional fragment thereof.

Abstract: The present invention relates to an in vitro method for identifying a molecule, which interferes with the interaction between a glial cell-line derived neurotrophic factor family ligand (GFL) and a heparan sulfate proteoglycan (HSPG), by screening a library of molecules against a matrix anchored complex comprising at least one immobilized glial cell-line derived neurotrophic factor family ligand (GFL) and at least one heparan sulfate proteoglycan (HSPG), wherein the interfering molecule is isolated based on its capacity to replace a glial cell-line derived neurotrophic factor family ligand (GFL) in said anchored complex. The invention also relates to a complex for identifying such a molecule. The invention also relates to methods for preventing or delaying a neurodegenerative process as well as to method for prophylactic treatment or treatment of a disorder in the nervous system.

Abstract: The present invention relates to the use of oligonucleotides having modified nucleobases to inhibit gene expression and/or replication of viruses in a subject. The modified nucleobases may be mercapto-modified bases or hydroxy-modified nucleobases. It is contemplated that the oligonucleotides further comprise a nuclease complex which enhances anti-viral activity of the oligonucleotides.

Abstract: The invention is concerned with the use of oligonucleotide analogs that contain specifically modified DNA bases to be used in hybridization of nucleic acids, polymerase chain reaction (PCR) and siRNA-mediated gene silencing (RNAi).

Abstract: The present invention relates to Glial Cell Line-Derived Neurotrophic Factor (GDNF) protein and gene and is, in particular, directed to a novel splice variant of GDNF protein, which is encoded by a novel splice variant pre-(?)pro-GDNF, and secreted under biological regulation.

Abstract: The present invention discloses a novel neurotrophic factor protein, MANF2 and a genetic sequence encoding the same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of MANF2 dependent conditions. The molecule of the present invention is also a useful effector of primary and central neurons, especially dopaminergic neurons at the central nervous system and growth factor genes.

Abstract: Methods for preventing or treating damage to sensory hair cells and cochlear neurons are disclosed. The methods comprise the administration of an effective amount of a compound of Formula I or Formula II. The method provides for the prevention/treatment of both hearing loss and loss of the sense of balance.

Abstract: The present invention provides compounds having a chelating moiety and an oligonucleotide sequence wherein the oligonucleotide includes one or more modified nucleobases, such as hydroxynucleobases. The disclosed compounds are suitable for antisense therapy. The chelating moiety can be complexed to an ion of a lanthanide metal. These compounds are efficient translation inhibitors of nucleic acids and have increased binding affinity for target nucleic acids. The invention also includes compositions and methods of using these compositions as antisense therapy.

Abstract: The invention provides methods and compositions for identifying agents which modulate cell death, indicated e.g. by the expression of caspase-2 and/or caspase-7, in GDNF family growth factor deprived neuronal or nonneuronal cells. The methods for identifying such agents find particular application in drug development.

Abstract: The present invention generally relates to the field of treatment of neuronal disorders and more particularly to neurotrophic factor MANF and uses thereof. The present invention provides a pharmaceutical compound comprising MANF nucleic acid molecule, MANF protein or a functional fragment thereof for the treatment of a peripherial neuropathy including Alzheimer's disease, Parkinson's disease, epilepsy, drug addiction and ischemic brain injury.

Abstract: The present invention discloses purified and isolated nucleic acid sequences encoding polypeptides having a structure substantially similar to that of splicing forms of mammalian GFR?4 comprising the amino acid sequence (SEQ ID NO:1:)-(SEQ ID NO:6:). The preferred sequences comprise cDNAs having the sequence (SEQ ID NO:7:)-(SEQ ID NO:13:). The present invention is also related to purified and isolated polypeptides comprising the amino acid sequence and or substantially similar splicing forms of mammalian GFRà4. Furthermore, the invention is related to substances capable of specifically recognizing said polypeptides and including both antibodies and receptors. The active compounds of the present invention including cDNAS, polypeptides, binding substances, and antibodies.

Abstract: The present invention discloses a novel neurotrophic factor protein, MANF2 and a genetic sequence encoding the same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of MANF2 dependent conditions. The molecule of the present invention is also a useful effector of primary and central neurons, especially dopaminergic neurons at the central nervous system and growth factor genes.

Abstract: The present invention discloses a novel neurotrophic factor protein, MANF2 and a genetic sequence encoding the same. The molecule will be useful in the development of a range of therapeutics and diagnostics useful in the treatment, prophylaxis and/or diagnosis of MANF2 dependent conditions. The molecule of the present invention is also a useful effector of primary and central neurons, especially dopaminergic neurons at the central nervous system and growth factor genes.