The present invention relates to a composition for preventing, improving or treating muscle atrophy, which includes Gryllus bimaculatus, and more particularly, a Gryllus bimaculatus powder or Gryllus bimaculatus protein extract, as an active ingredient, and a method of preparing the same. The composition according to the present invention is effective in inhibiting the expression of muscle atrophy-associated key transcription factors, such as FoxO3 and MuRF-1, and is expected to be effectively used in muscle atrophy, various diseases caused thereby, muscle aging, undernourished patients, growing children and the elderly.

Described herein are polypeptides comprising an IGF2 amino acid sequence and an amino acid sequence from a heterologous polypeptide useful for the treatment of soft-tissue and muscle diseases, disorders, and injuries. Mutations within the IGF2 amino acid sequence improved the stability of the molecule by reducing backbone cleavage. Also described herein are synergistic combinations of an Insulin-like Growth Factor 1 Receptor (IGF1R) agonist and a short chain fatty acid. Also described are methods of treating muscle and soft-tissue diseases comprising administering the polypeptides and/or synergistic compositions.

Described herein are polypeptides comprising an IGF2 amino acid sequence and an amino acid sequence from a heterologous polypeptide useful for the treatment of soft-tissue and muscle diseases, disorders, and injuries. Mutations within the IGF2 amino acid sequence improved the stability of the molecule by reducing backbone cleavage. Also described herein are synergistic combinations of an Insulin-like Growth Factor 1 Receptor (IGF1R) agonist and a short chain fatty acid. Also described are methods of treating muscle and soft-tissue diseases comprising administering the polypeptides and/or synergistic compositions.

Method for treating a disease, condition, or syndrome in a subject comprising administering, to a subject in need thereof, a solid or liquid pharmaceutical composition comprising: (a) a high purity botulinum neurotoxin or a complex comprising botulinum neurotoxin, wherein the botulinum neurotoxin is of type A, B, C, D, E, F or G; and (b) a surfactant;
wherein the composition does not comprise albumin or a polysaccharide.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

Provided herein are methods for decreasing blood-brain barrier permeability in a subject with a neuroinflammatory disorder, comprising administering to the subject an effective amount of an isolated binding molecule which specifically binds to semaphorin-4D (SEMA4D) or to its high affinity Plexin-B1 receptor.

Provided are novel compounds of Formula (I): ##STR00001##
pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.

The present invention pertains to an inventive release mechanism for extracellular vesicle (EV)-mediated intracellular and intramembrane delivery of therapeutic polypeptides. More specifically, the invention relates to EVs comprising polypeptide constructs which comprise a therapeutic polypeptide releasably attached to an exosomal polypeptide. Furthermore, the present invention pertains to manufacturing methods, pharmaceutical compositions, medical uses and applications, and various other embodiments related to the inventive EVs.

Angelman Syndrome (AS) is a genetic disorder occurring in approximately one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.

The present invention relates to 7-(4,7-diazaspiro[2.5]octan-7-yl)-2-(2,8-dimethylimidazo[1,2-b]pyridazin-6-yl)pyrido[1,2-a]pyrimidin-4-one for use in the treatment of spinal muscular atrophy (SMA), its pharmaceutical composition to be used in the treatment of SMA, its methods of treatment thereof.