Abstract: The present invention relates to pharmaceutical formulations of Aviptadil and its derivatives. The stability of the Aviptadil formulation was shown to be improved by a formulation having a defined concentration of Aviptadil prepared in a buffer having a defined pH range.

Abstract: Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Abstract: The following class of molecule is disclosed: a dimer containing a first neublastin polypeptide and a second neublastin polypeptide, wherein: (a) at least one of the polypeptides is glycosylated; (b) at least one of the polypeptides is conjugated at its N-terminus to a water-soluble synthetic polymer; and (c) neither of the polypeptides is conjugated to a water-soluble synthetic polymer at a position other than the N-terminus. Such dimers possess the biological activity of wild-type neublastin while displaying enhanced serum half-life and enhanced potency relative to wild-type neublastin.

Abstract: This invention relates to the use of ADNF polypeptides in the treatment of neurotoxicity induced by chemical agents or by disease processes. The ADNF polypeptides include ADNF I and ADNF III (also referred to as ADNP) polypeptides, analogs, subsequences such as NAP and SAL, and D-amino acid versions (either wholly D-amino acid peptides or mixed D- and L-amino acid peptides), and combinations thereof which contain their respective active core sites.

Abstract: The invention features methods and kits for treating or inhibiting the development of Parkinson's Disease by administering 7-chloro-4-aminoquinoline compounds, e.g., amodiaquine or glafenine. Stem cells are also useful in the methods of the invention and may be administered separately from or together with 7-chloro-4-aminoquinoline compounds. The invention further features methods of identifying additional chemical compounds that are useful in the treatment or inhibition of the development of Parkinson's Disease.

Abstract: The invention relates to T. cruzi trans-sialidase (TS) and to the neurotrophic and IL-6 secretion-inducing activities of the protein. TS, neurotrophic variants and/or neurotrophic peptides based upon the sequence of TS can be administered to a mammal to directly or indirectly provide neurotrophic support for neurons. A mammalian neurotrophic factor (e.g., CNTF, LIF) can be co-administered with the TS, neurotrophic variant and/or neurotrophic peptide. TS, IL-6 secretion-inducing variants and/or IL-6 secretion-inducing peptides based upon the sequence of TS can be administered to a mammal to induce the secretion of IL-6. TS, active variants and/or active peptides can be administered to a mammal having an acquired or congenital condition characterized by neuronal degeneration or to a mammal that has experienced trauma to the brain, spinal cord or peripheral nerves. The invention also relates to neurotrophic and IL-6 secretion-inducing variants of TS and to neurotrophic and IL-6 secretion-inducing peptides.

Abstract: The present invention provides a metastin derivative in which the amino acids comprising metastin were modified by alternative chemical substituents resulting in metastin derivitives, having excellent blood stability and exhibiting cancer metastasis inhibiting action or cancer growth inhibiting action.

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: Compositions and methods for the treatment of neuropathic pain are provided. Compositions of the invention may comprise proteins with a zinc-finger domain fused to a regulatory domain that is capable of either activating or repressing the expression of a target gene involved in neuropathic pain. Alternatively, compositions of the invention may comprise a nucleic acid sequence encoding a protein of the invention, which nucleic acid sequence may optionally be provided as a plasmid or within a virus or other vector for delivery to a target cell or tissue. Methods of treating neuropathic pain involving treatment of subject with the compositions of the invention are also provided. Exemplary target genes for the treatment of neuropathic pain include VR1, NaV1.8, and TrkA.

Abstract: This invention provide to a pharmaceutical composition for treating spinocerebellar ataxia (or atrophy, degeneration) or multiple system atrophy, or for improving ataxia or equilibrium disturbance comprising a compound of the formula (I): wherein R is methyl, cyano or carbamoyl, a pharmaceutically acceptable salt, or a solvate thereof as an active ingredient.

Abstract: The present invention relates to antibodies and related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention also relates to methods and compositions for detecting or diagnosing a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate function of B Lymphocyte Stimulator comprising antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator expression or inappropriate B Lymphocyte Stimulator function comprising administering to an animal an effective amount of one or more antibodies or fragments or variants thereof or related molecules that immunospecifically bind to B Lymphocyte Stimulator.

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: A conjugate comprises: (a) a mitochondrial membrane-permeant peptide; (b) an active agent or compound of interest such as a detectable group or mitochondrial protein or peptide; and (c) a mitochondrial targeting sequence linking said mitochondrial membrane-permeant peptide and said active mitochondrial protein or peptide. The targeting sequence is one which is cleaved within the mitochondrial matrix, and not cleaved within the cellular cytoplasm, of a target cell into which said compound is delivered. Methods of use of such compounds are also described.

Abstract: Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well established key role. DAPTA, a gp120-derived CCR5 entry-inhibitor has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We disclose here that as a stabilized analog of DAPTA, the short peptide All D TTNYT exhibits potent antagonism for both CCR2 (IC50 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. Oral administration of All D TTNYT (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia following partial ligation of the sciatic nerve in rats. Administered from day 8 to day 12, All D TTNYT (0.2-1 mg/kg) reverses already established hypersensitivity. All D TTNYT relieves pain hypersensitivity probably through either or both CCR2 and CCR5, since by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain.

Abstract: Compositions and methods for protecting neural tissue (e.g., neurons) from anoxia and spreading depression (SD) involve inhibiting the cGMP-dependent protein kinase (PKG) pathway. It was discovered that the PKG pathway plays a crucial role in regulating SD and tolerance to anoxia in the central nervous system (CNS). Inhibition of the PKG pathway greatly reduces SD and increases tolerance to anoxia (i.e., hypoxia), while activation of the pathway exacerbates SD pathology. The compositions and methods can be used to treat any condition associated with SD or anoxia, including stroke, spinal cord injury, neurogenerative disease, dizziness, headaches, and migraines.

Abstract: An antioxidant compound is disclosed.

Abstract: The present invention relates generally to a method for modulating cell survival. Modulation of cell survival includes inducing, enhancing or otherwise promoting cell survival such as the survival of neural cells as well as facilitating cell death such as the death of targeted cancer cells. The modulation of cell survival is mediated by a region identified on the p75 neurotrophin receptor (p75NTR) required for death signalling. The present invention further provides genetic molecules which encode the death signalling region of p75NTR which are useful in antagonising death signal function as well as promoting cell death when expressed in targeted cells. The present invention also contemplates recombinant peptides, polypeptides and proteins as well as chemical equivalents, derivatives and homologues thereof which comprise the death signalling portion of p75NTR. Particularly useful molecules of the present invention comprise peptides corresponding to soluble forms of the death signalling portion of p75NTR.

Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1.

Abstract: The present invention provides a method for preventing or treating opiate tolerance and dependence by administering to an individual in need of such treatment with a pharmaceutically effective amount of a blocking reagent for ephrinB-EphB signaling. The opiate tolerance and dependence can be caused by chronic morphine treatment and withdrawal. The blocking reagent can be an EphB receptor blocker such as EphB1-Fc and EphB2-Fc.

Abstract: Devices and methods for treating defects in peripheral nerves are provided. The devices can include acellular arterial tissue matrices that facilitate regrowth of nerve tissue across a gap or defect in a peripheral nerve.

Abstract: Disclosed are compositions and methods for treating Guillain-Barré syndrome (GBS) in a subject that involves neutralizing specific pathogenic anti-glycolipid antibodies in the circulation of the subject. This can involve administering to the subject a molecular mimic of a ganglioside that serves as a specific competitive inhibitor for anti-ganglioside antibodies in the circulation. Also disclosed is an animal model of GBS having anti-ganglioside antibodies in the circulation.

Abstract: The present invention relates to a method of protecting cells against damage caused at least in part by apoptosis, comprising administering to subjects a therapeutic dose of leumorphin having cytoprotective activity, and a pharmaceutical composition comprising an effective amount of leumorphin having a cytoprotective activity.

Abstract: The present invention relates to the field of therapeutic use of proteins, genes and cells, in particular to the therapy based on the biological function of a secreted therapeutic protein, METRNL, in particular for the treatment of disorders of the nervous system. METRNL is a Nerve Survival and Growth factor with neuroprotective and/or neurogenesis effects.

Abstract: A novel class of embryo derived peptides are described (Preimplantation factor) that were generated synthetically and were tested on peripheral blood immune cells and shown to block activated but not basal immunity, inhibiting cell proliferation and creating a TH2 type cytokine bias, in addition PIF enhance endometrial receptivity by increasing adhesion molecules expression. PIF biological activity appears to be exerted by specific binding to inducible receptors present on the several white cell lineages. PIF peptides, which are immune modulators therefore may have diagnostic and non toxic therapeutic applications in improving fertility, reducing pregnancy loss as well may be useful when administered for the treatment of autoimmune diseases and for prevention xenotransplants rejection.

Abstract: Embodiments of this invention include synthetic compounds (NRP analogues) of peptides termed neural regeneration peptides (NRPs). NRP analogues are made by substituting amino acids in the native peptide sequence, modifying amino acids chemically, by replacing amino acids with synthetic moieties, by stabilizing ?-turns, acetylation of terminal glycine residues or by cyclization. NRP analogues can be used to treat a variety of conditions involving degeneration of neural cells, and includes treating disorders of the nervous system, including peripheral neuropathy, multiple sclerosis, diabetic peripheral neuropathy, neurotoxin-induced neurodegeneration, and amyotrophic lateral sclerosis.

Abstract: Disclosed herein are methods and compositions for treating neuropathies by modulating endogenous NT-3 of GDNF gene expression.

Abstract: The present invention is based on the discovery that suppressing the activity of the Nogo receptor (NgR) alone does not result in extensive axon regeneration unless the intrinsic growth program of neurons is also activated. Accordingly, the present invention is directed to methods of stimulating axon regeneration using a combination therapy wherein agents that inhibit NgR activity or downstream pathways activated by inhibitory signals are combined with agents that activate the growth pathway of neurons (e.g. polypeptide growth factors, activators of macrophages, purine nucleosides, or hexoses).

Abstract: The presently described subject matter relates to isolated spider venom peptides, which are used as potent and selective ion channel blockers, and to a composition and methods for treatment of pain.

Abstract: The invention relates to the use of a homeoprotein of the bicoid family, in particular of the Otx family, for enhancing the survival of cultivated retinal ganglion neurones, and for preventing or treating ganglion neuron degeneration particularly occurring in glaucoma.

Abstract: A novel class of peptide ?-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA2-AA1-CO—NH—(CH2)n—R3. Processes for the synthesis of peptidyl ?-ketoamide derivatives.

Abstract: The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2).

Abstract: The present invention relates to the identification and use of bone morphogenetic protein (BMP)-binding domains of members of the repulsive guidance molecule (RGM) protein family, and polypeptide fragments and fusion proteins derived therefrom. The domains, i.e., peptide fragments and fusion proteins, according to the invention are suitable as agents for the active or passive immunization of individuals, or as diagnostic and therapeutic agents for use for diseases or medical conditions in whose origin or progression a member of the RGM family and a cellular receptor associated with this molecule, such as neogenin and/or BMP in particular, is involved. The invention further relates to monoclonal and polyclonal antibodies directed against the binding domains according to the invention, and against the polypeptides derived therefrom, and to methods for producing the polypeptides, fusion proteins, and antibodies according to the invention.

Abstract: The present invention relates to a method for treating, preventing or ameliorating a chronic neurodegenerative disorder, in particular progressive muscular atrophy (PMA), said method comprising administering to a subject in need of such a treatment, prevention or amelioration a specific inhibitor of a caspase I-dependent cytokine. Also specific inhibitors of a caspase I-dependent cytokine for treating, preventing or ameliorating a neurodegenerative disorder, in particular PMA, are disclosed herein. Furthermore, the present invention provides for the use of (a) specific inhibitor(s) of a caspase I-dependent cytokine in the medical or pharmaceutical intervention of neurodegenerative disorders.

Abstract: The present invention provides a method of modulating calcineurin activity in a cell by contacting the cell with at least one ApoE analog. Methods of treating various disorders associated with calcineurin activity using one or more ApoE analogs are also disclosed. In particular, the present invention provides a method of reducing demyelination and promoting remyelination in a subject. Methods of treating spinal cord or nerve injury in a subject are also described.

Abstract: The invention relates to neublastin neurotrophic factor polypeptides, nucleic acids encoding neublastin polypeptides, and antibodies that bind specifically to neublastin polypeptides, as well as methods of making and methods of using the same.

Abstract: The invention provides a method for suppressing the development of or treating neuropathic pain in a subject comprising administering to the subject an effective amount of a peptide of the formula: X1—X2—X3 (I) or X1—X2 (II) wherein X1 is an aromatic amino acid residue or is selected from the group consisting of 2-amino-hexanoic acid, 2-amino-heptanoic acid; 2-amino-octanoic acid; cyclohexyl-substituted 2-amino-ethanoic acid, cyclohexyl-substituted 2-amino-propanoic acid or 2-amino-butanoic acid and methionine; X2 is an acidic amino acid; and in Formula (I), X3 is 1 to 3 amino acid residues which are the same or different and are aliphatic amino acid residues and the C-terminal amino acid is optionally amidated. These peptides may be used to treat a nerve injury or a spinal cord injury or to improve chronic neurological outcome after such injuries.

Abstract: We describe the involvement of JunD in the activation of macrophages and the association of JunD in inflammatory diseases and conditions.

Abstract: 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.