Single chain polypeptide fusion protein, comprising: a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin targeting moiety; a protease cleavage site; a translocation domain; a first spacer located between the non-cytotoxic protease and the protease cleavage site; and a second spacer located between the galanin targeting moiety and the translocation domain.

A single chain polypeptide fusion protein, comprising: a non-cytotoxic protease capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent; a galanin targeting moiety; a protease cleavage site at which site the fusion protein is cleavable by a protease; a translocation domain capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent; a first spacer located between the non-cytotoxic protease and the protease cleavage site; and a second spacer located between the galanin targeting moiety and the translocation domain.

A single chain, polypeptide fusion protein, comprising: a non-cytotoxic protease, which protease is capable of cleaving a protein of the exocytic fusion apparatus of a nociceptive sensory afferent (eg clostridial neurotoxin L-chain or IgA protease); a galanin Targeting Moiety that is capable of binding to a Binding Site on the nociceptive sensory afferent, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the nociceptive sensory afferent (eg GALR1, GALR2, or GALR3 receptor); a protease cleavage site at which site the fusion protein is cleavable by a protease, wherein the protease cleavage site is located between the non-cytotoxic protease and the galanin Targeting Moiety; a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the nociceptive sensory afferent (eg HN domain of clostridial neurotoxin); a first spacer located between the non-cytotoxic protease and the protease cleavage site, wherein said first spacer comprises an amino acid sequence of from 4 to 25 amino acid residues; and a second spacer located between the galanin Targeting Moiety and the translocation domain, wherein said second spacer comprises an amino acid sequence of from 4 to 35 amino acid residues. Nucleic acid sequences encoding the polypeptide fusion proteins, methods of preparing same and uses thereof are also described (eg of treating, preventing or ameliorating pain).

The invention provides a polypeptide, for use in suppressing or treating itch, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an itch-specific DRG neuron or a pruriceptor; a Targeting Moiety (TM) that is capable of binding to a Binding Site on the itch-specific DRG neuron or a pruriceptor, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the itch-specific DRG neuron or a pruriceptor, and wherein said itch-specific DRG neuron or a pruriceptor expresses said SNARE protein; and a translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the itch-specific DRG neuron or a pruriceptor; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.

The present disclosure relates to a truncated form of IgA protease, a fusion protein comprising a truncated form of IgA protease (e.g., a fusion protein comprising a truncated form of IgA protease and Fc) and uses thereof in treating diseases associated with IgA deposition (e.g., IgA nephropathy).