INHIBITION OF SECRETION FROM NON-NEURONAL CELLS
The present invention relates to treatment of disease by inhibition of cellular secretory processes, to agents and compositions therefor, and to manufacture of those agents and compositions. The present invention relates particularly, to treatment of disease dependent upon the exocytotic activity of endocrine cells, exocrine cells, inflammatory cells, cells of the immune system, cells of the cardiovascular system and bone cells.
1 . A method of suppressing hypersecretion from an endocrine cell in a patient in need thereof, said method comprising:
administering an effective amount of a modified clostridial neurotoxin to said patient;
wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin in which the neuronal targeting activity of the clostridial neurotoxin has been removed; and
wherein said modified clostridial neurotoxin is covalently linked to a peptide that binds the modified clostridial neurotoxin to a binding site present on said endocrine cell.
2 . The method according to claim 1 , wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin in which the H C binding ability of the clostridial neurotoxin has been removed.
3 . The method according to claim 1 , wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin L-chain and a clostridial toxin translocation domain.
4 . The method according to claim 3 , wherein said clostridial toxin translocation domain is provided by a clostridial neurotoxin H-chain having a carboxy-terminal half and an amino-terminal half, wherein the neuronal targeting activity of the carboxy-terminal half of the H-chain has been removed.
5 . The method according to claim 3 , wherein said clostridial toxin translocation domain comprises the amino-terminal half of a clostridial neurotoxin H-chain.
6 . The method according to claim 3 , wherein said clostridial neurotoxin L-chain and said clostridial toxin translocation domain are present in the form of a di-chain in which the clostridial neurotoxin L-chain is covalently bonded to the clostridial toxin translocation domain.
7 . The method according to claim 1 , wherein the endocrine cell is a pituitary cell, and wherein the modified clostridial neurotoxin binds to said pituitary cell.
8 . The method according to claim 1 , wherein the patient suffers from acromegaly.
9 . The method according to claim 1 , wherein the patient suffers from Cushings disease.
10 . The method according to claim 1 , wherein the patient suffers from endocrine neoplasia.
11 . The method according to claim 1 , wherein the patient suffers from hyperprolactinaemia.
12 . A method of suppressing hypersecretion from an inflammatory cell in a patient in need thereof, said method comprising;
administering an effective amount of a modified clostridial neurotoxin to said patient;
wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin in which the neuronal targeting activity of the clostridial neurotoxin has been removed; and
wherein said modified clostridial neurotoxin is covalently linked to a peptide that binds the modified clostridial neurotoxin to a binding site present on said inflammatory cell.
13 . The method according to claim 12 , wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin in which the H C binding ability of the clostridial neurotoxin has been removed.
14 . The method according to claim 12 , wherein the modified clostridial neurotoxin comprises a clostridial neurotoxin L-chain and a clostridial toxin translocation domain.
15 . The method according to claim 14 , wherein said clostridial toxin translocation domain is provided by a clostridial neurotoxin H-chain having a carboxy-terminal half and an amino-terminal half, wherein the neuronal targeting activity of the carboxy-terminal half of the H-chain has been removed.
16 . The method according to claim 14 , wherein said clostridial toxin translocation domain comprises the amino-terminal half of a clostridial neurotoxin H-chain.
17 . The method according to claim 14 , wherein said clostridial neurotoxin L-chain and said clostridial toxin translocation domain are present in the form of a di-chain in which the clostridial neurotoxin L-chain is covalently bonded to the clostridial toxin translocation domain.
18 . The method according to claim 12 , wherein the inflammatory cell is an inflammatory cell selected from the group consisting of a mast cell, an eosinophil, a macrophage, a monocyte, a neutrophil, and a fibroblast; and
wherein the modified clostridial neurotoxin binds to said inflammatory cell.
19 . The method according to claim 12 , wherein the patient suffers from an allergy.
20 . The method according to claim 12 , wherein the patient suffers from asthma.