Abstract: The invention provides TrkB agonist antibodies or antigen-binding fragments that specifically enhance TrkB signaling activities. The invention also provides therapeutic methods of using such antibodies for promoting survival and regeneration of retinal ganglion cells, and for treating or preventing subjects suffering from or at risk of developing various neurodegenerative conditions such as glaucoma.

Abstract: The present invention provides methods for generating functional derivatives of effector polypeptides (e.g., hormones and receptor ligands) embedded in a different protein scaffold (e.g., antibody scaffolds). The methods involve modifying the effector polypeptide with a combinatorial library of terminal linker sequences, inserting the modified sequences into the host scaffold, and then selecting functional derivatives from the library of modified polypeptide sequences embedded in the host scaffold. As exemplifications, the invention also provides specific functional derivatives of leptin, scFSH and scRelaxin embedded in an antibody scaffold, as well as therapeutic applications of such functional fusion molecules.

Abstract: The invention provides TrkB agonist antibodies or antigen-binding fragments that specifically enhance TrkB signaling activities. The invention also provides therapeutic methods of using such antibodies for promoting survival and regeneration of retinal ganglion cells, and for treating or preventing subjects suffering from or at risk of developing various neurodegenerative conditions such as glaucoma.

Abstract: The present invention provides methods for generating functional derivatives of effector polypeptides (e.g., hormones and receptor ligands) embedded in a different protein scaffold (e.g., antibody scaffolds). The methods involve modifying the effector polypeptide with a combinatorial library of terminal linker sequences, inserting the modified sequences into the host scaffold, and then selecting functional derivatives from the library of modified polypeptide sequences embedded in the host scaffold. As exemplifications, the invention also provides specific functional derivatives of leptin, scFSH and scRelaxin embedded in an antibody scaffold, as well as therapeutic applications of such functional fusion molecules.

Abstract: The present invention relates to neurotrophin-3 (NT-3), a newly discovered member of the BDNF gene family. It is based, in part, on the identification of regions of nucleic acid sequence homology shared by BDNF and NGF (U.S. patent application Ser. No. 07/400,591, filed Aug. 30, 1989, incorporated by reference herein). According to the present invention, these regions of homology may be used to identify new members of the BDNF/NGF gene family; such methodology was used to identify NT-3. The present invention provides for the genes and gene products of new BDNF/NGF related neurotrophic factors identified by these methods. According to the invention, NT-3 may be used in the diagnosis and/or treatment of neurologic disorders, including, but not limited to, Alzheimer's disease and Parkinson's disease. Because NT-3 has been observed to exhibit a spectrum of activity different from the spcificities of BDNF or NGF, NT-3 provides new and valuable options for enducing regrowth and repair in the central nervous system.

Abstract: Modified ciliary neurotrophic factors and methods for their production and therapeutic use, especially in the treatment of Huntington's disease.

Abstract: Infusions of brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4 are used to produce analgesia in mammals. In addition, these neurotrophins are used to treat other diseases or disorders mediated by serotonin.

Abstract: The present invention is broadly directed to treatment of an addictive disease or disorder. In particular, the invention relates to inhibiting or reversing the biochemical and neurophysiological changes that correlate with behavioral changes of addictive diseases or disorders. The method of the invention comprises administering to a subject suspected of suffering from an addictive disease or disorder an amount of brain-derived factor (BDNF) or neurotrophin-4 (NT-4), or both, effective to reverse behavioral changes that are associated with the addictive disease or disorder. In a specific Example, administration of BDNF or NT-4 inhibits or reverses increased expression of tyrosine hydroxylase and glial ibrillary acidic protein in the ventral tegmental area of the brain, and inhibits or reverses increased levels of cyclic-AMP-dependent protein kinase activity in the nucleus accumbens.

Abstract: The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors.

Abstract: The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors.