Abstract: A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibers. They comprise a galactose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (L) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain, particularly chronic pain.

Abstract: In this application is described substrates for high-throughput assays of clostridial neurotoxin proteolytic activities. Two types of substrates are described for use in assays for the proteolytic activities of clostridial neurotoxins: (1) modified peptides or proteins that can serve as FRET substrates and (2) modified peptides or proteins that can serve as immobilized substrates. In both types a fluorescent molecules is present in the substrate, eliminating the requirement for the addition of a fluorigenic reagent. The assays described can be readily adapted for use in automated or robotic systems.

Abstract: The present invention relates to methods for treating neurogenic inflammation pain. The methods include administering an effective amount of a composition which includes a botulinum toxin component and a substance P component to a patient, thereby treating the neurogenic inflammation pain.

Abstract: The present invention relates to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.

Abstract: An isolated, biologically active 33 kDa hemagglutinin purified from the type A Clostridium botulinum neurotoxin complex and its uses are described.

Abstract: Methods for determining the effect of a Clostridal toxin on muscle are disclosed. In particular, methods for determining a potency and/or diffusion of a toxin based on a nuclear index and/or the extent of muscle atrophy are disclosed.

Abstract: Methods for treating cardiac muscle disorders, such as cardiac arrhythmias, by administration of a neurotoxin to cardiac muscle are disclosed. Bradycardia can be alleviated for several months by a single intrapericardial or intracardiac injection or infusion of a botulinum toxin. Tachycardia can be alleviated by preganglionic sympathetic nervous system administration of a botulinum toxin.

Abstract: Method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of, Botulinum toxin types A, B, C, D, E, F and G.

Abstract: The present invention provides methods for improving blood supply through a grafted blood vessel. In some embodiments, the methods comprise the step of locally administering a botulinum toxin to the grafted blood vessel, thereby improving blood supply through the grafted blood vessel.

Abstract: Methods for treating an injured muscle by local administration of a neurotoxin, such as a botulinum toxin, to promote healing and/or to reduce the pain associated with an injured muscle.

Abstract: Methods for treating psychiatric disorders include intracranial administration of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin type A, to a human patient.

Abstract: Modified neurotoxin comprising neurotoxin including structural modification, wherein the structural modification alters the biological persistence, preferably the biological half-life, of the modified neurotoxin relative to an identical neurotoxin without the structural modification. The structural modification includes addition or deletion of a leucine-based motif or parts thereof. In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In another embodiment, methods of using the modified neurotoxin to treat biological disorders include treating autonomic disorders, neuromuscular disorders or pains.

Abstract: A method of treating a patient suffering from a disease, disorder or condition includes the administration to the patient of a therapeutically effective amount of botulinum toxin of a selected serotype until the patient experiences loss of clinical response to the administered botulinum toxin and thereafter administering to the patient a therapeutically effective amount of another botulinum toxin of a different serotype.

Abstract: Methods for treating a non-spasm caused pain by peripheral administration to a patient of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin.

Abstract: The present invention relates to methods for treating neurological-urological conditions. This is accomplished by administration of at least one neurotoxin.

Abstract: Methods for reducing appetite by oral administration of a Clostridial toxin, such as a botulinum toxin.

Abstract: The present invention relates to an agent comprising a neurotoxin, methods for making the agents and methods for treating endocrine disorders, for example gonadotrophin related illnesses. Preferably, the agent comprises at least a portion of a botulinum toxin.

Abstract: A method of treating migraine and other disorders associated with the release of certain neurotransmitters from sensory neurons includes the steps of preparing a medicament comprising Botulinum toxin type A as active-ingredient and applying the medicament transdermally to a human exhibiting symptoms associated with migraine or another sensory neuron related disorder. A pharmaceutical composition for transdermal application comprising Botulinum toxin type A as active-ingredient for administration to a human exhibiting symptoms of migraine or another sensory neuron related disorder is also provided.

Abstract: Methods for treating endocrine disorders and for inhibiting gametogenesis by intracranial administration to a human patient of a therapeutically effective amount of a neurotoxin, such as a botulinum toxin type A.

Abstract: Methods for treating the hypothyroidism of Hashimoto's thyroiditis by local administration of a Clostridial toxin, such as a botulinum toxin, to the thyroid gland of a patient.

Abstract: Methods and compositions for modulating neurite outgrowth in damaged neural endplates. Also disclosed are methods for introducing drugs, ribozymes, antisense oligonucleotides and defective receptor genes within neurons.

Abstract: The present invention relates to vaccine compositions comprising iron phosphate as adjuvant. This iron phosphate is in the form of particles, the size of which is between 0.01 &mgr;m and 300 &mgr;m; it can be obtained by mixing a solution of iron salt and of phosphate salt.

Abstract: A method for separating and purifying HA-positive progenitor toxin(s) (LL and/or L toxins) and HA-negative progenitor toxin (M toxin) from a Clostridium botulinum strain is provided. The method comprises applying a liquid containing both the HA-positive progenitor toxin(s) and the HA-negative progenitor toxin to a lactose column. Also provided is a method for separating and purifying neurotoxin (7S toxin) from HA-positive progenitor toxins, which comprises treating HA-positive progenitor toxins with an alkaline buffer and then applying the resulting liquid containing dissociated neurotoxin and non-toxic components to a lactose column. Activated pure HA-positive toxins (L and LL toxins) and neurotoxin are obtained by simple procedures.

Abstract: Natural and modified neurotoxins and isolated neurotoxin compositions are described. The neurotoxins may include one or more structural modifications, wherein the structural modification(s) alters the biological persistence, such as the biological half-life and/or a biological activity of the modified neurotoxin relative to an identical neurotoxin without the structural modification(s). In one embodiment, methods of making the modified neurotoxin include using recombinant techniques. In some embodiments, methods of using the modified neurotoxin to treat conditions include treating various disorders, neuromuscular ailments and pain.

Abstract: Methods of identifying compounds that inhibit the biological persistence of a Clostridial toxin are disclosed. Methods of identifying compounds that inhibit the enzymatic activity of Clostridial toxin are disclosed. Methods of identifying compounds that inhibit both the biological persistence and enzymatic activity of a Clostridial toxin are disclosed. Methods of identifying compounds that enhance the biological persistence of a Clostridial toxin are disclosed. Methods of identifying compounds that enhance the enzymatic activity of Clostridial toxin are disclosed. Methods of identifying compounds that enhance both the biological persistence and enzymatic activity of a Clostridial toxin are disclosed.

Abstract: A sinus headache can be treated by administration of a botulinum toxin to a patient. The botulinum toxin can be botulinum toxin type A and the botulinum toxin can be administered to or to the vicinity of a sinus membrane of a patient with a sinus headache.

Abstract: Behavioral pharmacological data with the compound of formula (I), a novel and selective 5HT2A/2C receptor inverse agonist, demonstrate in vivo efficacy in models of psychosis and dyskinesias. This includes activity in reversing MK-801 induced locomotor behaviors, suggesting that this compound may be an efficacious anti-psychotic, and activity in an MPTP primate model of dyskinesias, suggesting efficacy as an anti-dyskinesia agent. These data support the hypothesis that 5HT2A/2C receptor inverse agonism may confer antipsychotic and anti-dyskinetic efficacy in humans, and indicate a use of the compound of formula (I) and related agents as novel therapeutics for Parkinson's Disease, related human neurodegenerative diseases, and psychosis.

Abstract: Methods for treating a head banging disorder by local administration of a Clostridial toxin. The local administration can be by intramuscular, transdermal, intradermal or subdermal administration of a low dose of botulinum toxin.

Abstract: Methods for treating a hand washing disorder by local administration of a Clostridial toxin. The local administration can be by intramuscular, transdermal, intradermal or subdermal administration of a low dose of botulinum toxin.

Abstract: Methods for treating obsessions and compulsions by local administration of a Clostridial toxin. The obsessions or compulsions can be eye poking, body rocking, finger biting, counting, checking and related disorders treated by low dose, intramuscular administration of a botulinum toxin.

Abstract: Methods for treating trichotillomania by local administration of a Clostridial toxin. The local administration can be by intramuscular, transdermal, intradermal or subdermal administration of a low dose of botulinum toxin.

Abstract: Methods for treating a dermatillomania by local administration of a Clostridial toxin. The local administration can be by intramuscular, transdermal, intradermal or subdermal administration of a low dose of botulinum toxin.

Abstract: The present invention related to methods for treating neurological-urological conditions associated with prostate cancer or methods of treatment of prostate cancer, which is accomplished by administration of botulinum toxin to the patient.

Abstract: Chalazia and hordeola are the most common lesions occurring in the human eyelid, and often recurrences are managed by surgical intervention to remove fatty inclusions within the lid with associated inflammatory reaction. The present invention provides non-surgical methods of treating chalazia, hordeola and cutaneous infections comprising the administration of compositions comprising botulinum toxin. The present invention provides methods that effectively block meibum secretion from the meibomian glands, reduce sebaceous bacterial culture media on skin, and sebaceous secretion from the glands of Zeis. Decreased production of meibum and associated fatty substances resulting from the methods of the present invention, decrease gland blockage and tissue inspissations, resulting in reduced recurrence of chalazia, hordeola and related inflammatory reactions and lesions.

Abstract: A method for treating uterine disorders, including hyperplasic, hypertonic, cystic and/or neoplastic uterine gland tissue by local administration of a botulinum toxin to or to the vicinity of the afflicted uterine tissue.

Abstract: A hybrid protein (GFP-TTC) comprising the non-toxic proteolytic C fragment of tetanus toxin fused to green fluorescent protein was used to analyze the functional synaptic organization of neural networks. When injected intramuscularly in vivo, the GFP-TTC hybrid protein binds to tetanus neurotoxin receptors and clusters very rapidly to the active neuromuscular junction. Membrane traffic by GFP-TTC at the pre-synaptic level of the neuromuscular junction is strongly and rapidly influenced by exogenously co-injecting neurotrophic factors, such as BDNF, NT-4, and GDNF, but not by NGF, NT-3, and CNTF. The membrane traffic, directly detected using GFP-TTC in vivo, permits methods of analyzing synaptic functioning as well as methods of modulating neuronal transport using neurotrophic factors and agonists or antagonists thereof.

Abstract: A biodegradable botulinum toxin ocular implant for treating a medical condition of the eye upon implantation of the implant into the vitreous chamber of a patient's eye.

Abstract: Conjugates of transferrin or transcobalamin with anti-protozoan drugs are useful in the treatment of protozoan infections. Suitable anti-protozoan drugs include apoptosis inducing compounds, a cytotoxic antibiotic, an alkalating agent, a plant toxin, and a bacteria mutant toxin. Transferrin or transcobalamin is preferably coupled to the anti-protozoan drug by means of glutaraldehyde.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: A method for treating priapism in a mammal by administration of a botulinum toxin.

Abstract: Methods for treating the hypothyroidism of Hashimoto's thyroiditis by local administration of a neurotoxin, such as a botulinum toxin, to the thyroid gland of a patient.

Abstract: Botulinum toxin, a well know systemic poison, produces favorable therapeutic effect by virtue of regionally attaching to nerves within the myoneural junction and possibly other tissues in a target region of a particular tissue. The present invention provides compositions of botulinum toxin and a sequestration agent that increase sequestration and delivery of the botulinum toxin to neural and associated tissues, as compared with available formulations of botulinum toxins, and thereby produce a beneficial clinical effect. The sequestration agents of the present invention include proteins, lipids and carbohydrates. A preferred composition of the present invention comprises a botulinum toxin and an albumin. The present invention also provides methods of treating neuromuscular diseases and pain using the disclosed compositions and methods of making the disclosed compositions.

Abstract: The invention relates to the use of a composition, comprising a fusion protein and at least one transporter for the in-vivo inhibition of scar tissue formation, the in-vivo reduction of secondary damage and/or the in-vivo accumulation of macrophages. The fusion protein contains at least one binding domain for the transporter and at least one modulation domain for the covalent modification of small GTP-binding proteins. The transporter permits the uptake of the fusion protein in a target cell.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: Agents for treating pain, methods for producing the agents and methods for treating pain by administration to a patient of a therapeutically effective amount of the agent are disclosed. The agent may include a clostridial neurotoxin, a fragment or a derivative thereof, attached to a targeting component, wherein the targeting component is selected from a group consisting of compounds which selectively binds at the alpha-2B or alpha-2B/alpha-2C adrenergic receptor subtype(s) as compared to other binding sites, for example, the alpha-2A adrenergic receptor subtype.

Abstract: The present invention provides for methods of treating cardiovascular diseases in a mammal. The methods include a step of administering an effective amount of a botulinum toxin directly to a blood vessel of a mammal thereby treating a cardiovascular disease.

Abstract: The present invention is related to compositions and methods for the delivery of nucleic acids to neurons in a mammal, and uses thereof. The present invention specifically discloses the use of compounds that cause synaptic nerve sprouting to increase neuron retrograde transport of a vector or a product (a polypeptide or a nucleic acid for example) in a mammal. The invention is also based on the use of a compound that interacts with synaptosomal associated proteins to increase neuron retrograde transport of a vector or a product such as one cited above in a mammal. The invention also relates to a product comprising a viral vector comprising a transgene and a compound that causes synaptic nerve sprouting, for sequential use for delivering said transgene to neurons by retrograde transport and its uses for the preparation of a composition used as a treatment in several neurological disorders.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of Botulinum toxin types A, B, C, D, E, F and G.

Abstract: A method and composition for treating a patient suffering from a disease, disorder or condition and associated pain include the administration to the patient of a therapeutically effective amount of a neurotoxin selected from a group consisting of botulinum toxin types A, B, C, D, E, F and G.

Abstract: The invention relates to a vaccine formulation for the prevention of Haemophilus Influenzae Type B (Hib) infections and where the antigen is adsorbed onto aluminum phosphate. The invention also relates to a multivalent vaccines, that is a vaccine for the amelioration or treatment of more than one disease states. The present invention also relates to the production and use of such vaccines in medicine.