Methods and systems for delivering toxin and toxin fragments to a patient's nasal cavity provide for both release of the toxin and delivery of energy which selectively porates target cells to enhance uptake of the toxin. The use of energy-mediated delivery is particularly advantageous with light chain fragment toxins which lack cell binding capacity.

The present invention relates to the pharmaceutical field. Specifically, it contemplates a polynucleotide encoding a neurotoxin polypeptide exhibiting a reduced duration of the biological effect in a subject, wherein said polypeptide comprises at least one E3 ligase recognition motif in the light chain, wherein said E3 ligase recognition motif is preferably a binding motif for the E3 ligase MDM2. The invention further pertains to polypeptides encoded by the polynucleotide of the invention as well as polypeptides comprising one or more amino acid substitutions. Further encompassed by the present invention are vectors and host cells comprising the said polynucleotide, polypeptides encoded thereby and antibodies specifically binding to the polypeptides. Moreover, the invention relates to medicaments comprising said polynucleotides and polypeptides, as well as specific therapeutic applications thereof. Furthermore, the present invention contemplates methods for the manufacture of the polypeptides and medicaments.

Disorders such as headaches can be treated by administration of a botulinum toxin to a patient suffering therefrom, such as a migraine headache. A combined a fixed site/fixed dose and an optional follow the pain variable dosage and injection site paradigm is disclosed for optimizing clinical effectiveness of botulinum toxin administration for patients suffering headache, particularly chronic migraine.

The present specification discloses methods of treating a psychological trauma in an individual using botulinum toxins and/or a Targeted Exocytosis Modulator, and compositions thereof.

Methods for treating premature ejaculation and prolongation of climax time in a patient in need thereof by local administration of a Clostridial neurotoxin, such as a botulinum toxin, are provided.

Methods for treating a bladder dysfunction by injecting a clostridial derivative to a target site below the bladder midline are described.

Methods are provided for treating or preventing seasonal affective disorder caused by the onset of a specific season in a subject. The method include administering a therapeutically effective amount of a neurotoxin to a facial muscle to cause paralysis of the facial muscle, thereby affecting the ability of the subject to frown and thus treating or preventing the seasonal affective disorder prior to the onset of the season.

The invention relates to a solid or liquid pharmaceutical composition comprising botulinum neurotoxin complex (type A, B, C, D, E, F or G) or high purity botulinum neurotoxin (type A, B, C, D, E, F or G), and a surfactant. In particular the invention relates to a solid or liquid pharmaceutical composition comprising a crystalline agent.

The invention relates to a solid or liquid pharmaceutical composition comprising botulinum neurotoxin complex (type A, B, C, D, E, F or G) or high purity botulinum neurotoxin (type A, B, C, D, E, F or G), and a surfactant. In particular the invention relates to a solid or liquid pharmaceutical composition comprising a crystalline agent.

Methods of treating or preventing cancer, or treating or preventing noncancerous tumors or lesions, in a subject in need thereof. The methods involve administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject. In addition, methods of inhibiting or preventing glycolysis in cancer cells in a subject, promoting mitochondrial respiration in cancer cells in a subject, and promoting oxidative stress in cancer cells in a subject, by administering a therapeutically effective amount of one or more inhibitors of the YAP/TAZ pathway to the subject.