The City University of New York

Research Foundation of Cuny, Hunter College

Beth Israel Deaconess Medical Center, Inc.

Cornell University

Marie T Filbin

Rajiv R Ratan

Sari S Hannila

Zixuan Cao

Marco Domeniconi

The present invention relates to a method for enhancing arginase activity in a damaged or injured cell. In other aspects, the invention provides a method for treating a disorder that can be treated by enhancing arginase activity in a human in need thereof, the method comprising administering to the human an effective amount of a compound that enhances arginase activity. Such disorders include ischemia, hypoxia, neurodegenerative disease or condition, stroke or trauma of the nervous system. In yet another aspect, the invention provides methods for promoting regeneration of a neural cell in a human in need thereof.

Compounds for enhancing arginase activity and methods of using same

This invention relates to the novel identification of arginase as an enzymatic activity which can reverse inhibition of neuronal regeneration in the central and peripheral nervous system. Assays to monitor the effects of various agents on arginase expression and thus on neuronal regeneration and repair and to identify agents which will block or promote the inhibitory effects on neuronal outgrowth are provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of myelin on neural regeneration by affecting arginase activity or putrescine and derivative polyamine levels in a neuron. Methods for regulating and for promoting (or repressing) neuronal growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with conditions, disorders or diseases, comprising the step of administering at least one of the compositions according to this invention, are provided.

Methods for stimulating nervous system regeneration and repair by regulating arginase I and polyamine synthesis

This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

Protein transduction domains derived from secretory leukocyte protease inhibitor

The present invention provides methods for stimulating neuronal survival, growth and regeneration by administering SLPIs to animals, such as humans. These methods can be used to treat a variety of neurological conditions such as neural injuries and degenerative diseases in subjects in need thereof.

Stimulation of neuron regeneration by secretory leukocyte protease inhibitor

The present invention relates generally to products, compositions and methods useful for promoting neural repair and regeneration. The products and compositions of this invention include myelin-associated glycoprotein (MAG) derivatives that are inhibitors of endogenous MAG (e.g., mutant MAG proteins) and Nogo Receptor (NgR) binding inhibitors that are peptides derived from MAG, Nogo and OMgp that can bind to NgR and block NgR signaling. Peptides that can bind and activate NgR signaling are also provided. Inhibitory MAG derivatives and NgR binding inhibitors are useful for blocking the inhibition of neural regeneration mediated by proteins such as MAG, Nogo and/or OMgp in the nervous system. These inhibitors are also useful for treating neural degeneration associated with injuries, disorders or diseases.

Inhibitors of myelin-associated glycoprotein (MAG) activity for regulating neural growth and regeneration

This invention relates to the novel identification of myelin-associated glycoprotein (&ldquo;MAG&rdquo;) as a potent inhibitor of neural regeneration. More particularly, this invention relates to compositions and methods useful for reversing inhibition of neural regeneration in the central and peripheral nervous system. Assays to monitor the effects of MAG on neural regeneration and to identify agents which will block or promote the inhibitory effects of MAG on neural outgrowth are provided. Screening methods for identifying such agents are also provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of MAG on neural regeneration. Methods for regulating and for promoting neural growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with disorders or diseases, comprising the step of administering at least one of the compositions according to this invention are provided.

Compositions and methods using myelin-associated glycoprotein (MAG) and inhibitors thereof

Composition and methods using myelin-associated glycoprotein (MAG) and inhibitors thereof

This invention relates to the novel identification of myelin-associated glycoprotein ('MAG') as a potent inhibitor of neural regeneration. More particularly, this invention relates to compositions and methods useful for reversing inhibition of neural regeneration in the central and peripheral nervous system. Assays to monitor the effects of MAG on neural regeneration and to identify agents which will block or promote the inhibitory effects of MAG on neural outgrowth are provided. Screening methods for identifying such agents are also provided. This invention also relates to compositions and methods using agents that can reverse the inhibitory effects of MAG on neural regeneration. Methods for regulating and for promoting neural growth or regeneration in the nervous system, methods for treating injuries or damage to nervous tissue or neurons, and methods for treating neural degeneration associated with disorders or diseases, comprising the step of administering at least one of the compositions according to this invention are provided.

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New York, NY, United States of America

Marie T Filbin