THERAPEUTICS FOR SUPPRESSING OSTEOPOROSIS

摘要

The invention provides a polypeptide, for use in suppressing or treating osteoporosis, wherein the polypeptide comprises: a non-cytotoxic protease, which protease is capable of cleaving a SNARE protein in an enterochromaffin cell; a Targeting Moiety (TM) that is capable of binding to a Binding Site on an enterochromaffin cell, which Binding Site is capable of undergoing endocytosis to be incorporated into an endosome within the enterochromaffin cell, and wherein said enterochromaffin cell 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 enterochromaffin cell; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.

主权项

1. A polypeptide, for use in suppressing or treating osteoporosis, wherein the polypeptide comprises:
(i) a non-cytotoxic protease selected from a clostridial neurotoxin L-chain and an IgA protease, which protease is capable of cleaving a SNARE protein in an enterochromaffin cell; (ii) a Targeting Moiety that is capable of binding to a receptor selected from the group comprising: a VPAC receptor; a TGFβI receptor; a gamma-aminobutyric acid (GABA) receptor; fibroblast growth factor receptor; and a peptide YY (PYY) receptor on an enterochromaffin cell, which receptor is capable of undergoing endocytosis to be incorporated into an endosome within the enterochromaffin cell, and wherein said enterochromaffin cell expresses said SNARE protein; and (iii) a translocation domain comprising a clostridial neurotoxin translocation domain that is capable of translocating the protease from within an endosome, across the endosomal membrane and into the cytosol of the enterochromaffin cell; with the proviso that the polypeptide is not a clostridial neurotoxin (holotoxin) molecule.