The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1/OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1/OBR signaling pathway.

Polypeptides, and methods for their use, are disclosed that have an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO:1, are provided, wherein (a) the polypeptide degrades a PFQPQLPY (SEQ ID NO: 140) peptide and/or a PFPQPQQPF (SEQ ID NO: 68) at pH 4; (b) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp; and (c) the polypeptide comprises an amino acid change from SEQ ID NO: 1 at one or more residues selected from the group consisting of 221, 262E, 268, 269, 270, 319A, 320, 354E/Q/R/Y, 358S/Q/T, 368F/Q, 399, 402, 406, 424, 449, 461, 463, 105, 171, 172, 173, 174, and 456.

Polypeptides, and methods for their use, are disclosed that have an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO:1, are provided, wherein (a) the polypeptide degrades a PFQPQLPY (SEQ ID NO: 140) peptide and/or a PFPQPQQPF (SEQ ID NO: 68) at pH 4; (b) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp; and (c) the polypeptide comprises an amino acid change from SEQ ID NO: 1 at one or more residues selected from the group consisting of 221, 262E, 268, 269, 270, 319A, 320, 354E/Q/R/Y, 358S/Q/T, 368F/Q, 399, 402, 406, 424, 449, 461, 463, 105, 171, 172, 173, 174, and 456.

Compositions for promoting intestinal health are disclosed and described. In one example, the composition can include a combination of cyanidins and delphinidins, in an amount sufficient to treat intestinal hyperpermeability. In a further example, the composition can further comprise a prebiotic blend and fructooligosaccharides. Further presented herein, is a method of treating a condition or disorder related to gastrointestinal health in a subject. In one example, the method can include maximizing tight junction integrity in epithelial cells of gastrointestinal tract of the subject.

Compositions for promoting intestinal health are disclosed and described. In one example, the composition can include a combination of cyanidins and delphinidins, in an amount sufficient to treat intestinal hyperpermeability. In a further example, the composition can further comprise a prebiotic blend and fructooligosaccharides. Further presented herein, is a method of treating a condition or disorder related to gastrointestinal health in a subject. In one example, the method can include maximizing tight junction integrity in epithelial cells of gastrointestinal tract of the subject.

GLP-2 analogs, such as teduglutide, and fusion proteins of GLP-2 with immunoglobulin are administered before, during or after surgery, particularly resection of the small intestine. When short bowel syndrome develops after surgical resection of the small intestine, parenteral nutrition is usually necessary to compensate for reduced absorption of water and nutrients across the small intestine. GLP-2 analogs and GLP-2 fusion proteins promote growth of small intestine, improve nutrient absorption and can reduce the need for parenteral nutrition after surgery.

1H-pyrazolo[4,3-g]isoquinoline and 1H-pyrazolo[4,3-g]quinoline derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).

Pyrano[4,3-b]indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD)

Pyrrolo[2,3-f]indazole and 2,4,5,10-tetrazatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8,11-pentaene derivatives as alpha-l-antitrypsin modulators for treating alpha-l-antitrypsin deficiency (AATD)

Indole derivatives as alpha-1-antitrypsin modulators for treating alpha-1-antitrypsin deficiency (AATD).