Abstract: The Rho family of GTPases regulates axon growth and regeneration. Inactivation of Rho with C3, a toxin from Clostridium botulinum, can stimulate regeneration and sprouting of injured axons. The present invention provides novel chimeric C3-like Rho antagonists. These new antagonists are a significant improvement over C3 compounds because they are 3-4 orders of magnitude more potent to stimulate axon growth on inhibitory substrates than recombinant C3. The invention further provides methods of treating a disease of the eye by administering the compounds of the invention.

Abstract: The present invention relates to novel chimeric C3-like Rho antagonists and their use for promoting repair and neuron survival in injured mammalian central and peripheral nervous system and for treating or preventing cancer.

Abstract: Pharmaceutical compositions, each consisting of a cell-permeable fusion protein conjugate of a polypeptidic cell-membrane transport moiety and a Clostridium botulinum C3 exotransferase unit, or a functional analog thereof, are provided. The compositions are useful to prevent or inhibit uncontrolled proliferation, spreading, and migration of a metastatic neoplastic cell of a cancer in a mammal. The compositions can each effect or arrest combination of two or more of tumor cell proliferation, migration, angiogenesis, and metalloproteinase secretion.

Abstract: Substituted piperidine compounds represented by the structure I are provided, wherein each of R1a, R1b, R1c, R1d, R1e, R1f, R1g, R1h, R2, R2A, R3, R4, A, X, a, x and n is as defined in the specification. Substituted piperidine compounds of structure I may permeate or penetrate across a nerve cell membrane into the interior of a nerve cell, may inhibit intracellular Rho kinase enzyme found in nerve cells in mammals, and may find utility in repair of damaged nerves in the central and peripheral nervous system of such mammals. These compounds may induce the regeneration or growth of neurites in mammalian nerve cells and may thereby induce regeneration of damaged or diseased nerve tissue. These compounds also find additional utility as antagonists of the enzyme Rho kinase in treatment of disease states in which Rho kinase is implicated.

Abstract: The Rho family GTPases regulates axon growth and regeneration. Inactivation of Rho with C3, a toxin from Clostridium botulinum, can stimulate regeneration and sprouting of injured axons. The present invention provides novel chimeric C3-like Rho antagonists. The invention further provides evidence that these compounds promote repair when applied to the injured mammalian central nervous system, such as the retina. The present invention provide agents which are able to diffuse readily and therefore can promote repair for neurodegenerative disease of the eye, such as macular degeneration. The present invention further provides methods of treating macular degeneration, methods of inhibiting or reducing the rate of subretinal neovascularization and proliferation of neovascular tissue and methods of protecting retinal photoreceptor cell death.

Abstract: Substituted piperidine compounds represented by the structure I are provided, wherein each of R1a, R1b, R1c, R1d, R1e, R1f, R1g, R1h, R2, R2A, R3, R4, A, X, a, x and n is as defined in the specification. Substituted piperidine compounds of structure I may permeate or penetrate across a nerve cell membrane into the interior of a nerve cell, may inhibit intracellular Rho kinase enzyme found in nerve cells in mammals, and may find utility in repair of damaged nerves in the central and peripheral nervous system of such mammals. These compounds may induce the regeneration or growth of neurites in mammalian nerve cells and may thereby induce regeneration of damaged or diseased nerve tissue. These compounds also find additional utility as antagonists of the enzyme Rho kinase in treatment of disease states in which Rho kinase is implicated.

Abstract: The Rho family GTPases regulates axon growth and regeneration. Inactivation of Rho with C3, a toxin from Clostridium botulinum, can stimulate regeneration and sprouting of injured axons. The present invention provides novel chimeric C3-like Rho antagonists. These new antagonists are a significant improvement over C3 compounds because they are 3-4 orders of magnitude more potent to stimulate axon growth on inhibitory substrates than recombinant C3. The invention further provides evidence that these compounds promote repair when applied to the injured mammalian central nervous system.