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OwnerKeith Foster, John Chaddock +2inventors
InventorsKeith Foster, John Chaddock, Conrad Quinn, John Purkiss
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A method of treatment of disease by inhibition of cellular secretory processes is provided. The method has particular application in the treatment of diseases 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. Agents and compositions therefor, as well as methods for manufacturing these agents and compositions, are provided. In a preferred embodiment a clostridial neurotoxin, substantially devoid of holotoxin binding affinity for neuronal cells of the presynaptic muscular junction, is associated with a targeting moiety. The targeting moiety is selected such that the clostridial toxin conjugate so formed may be directed to a non-neuronal target cell to which the conjugate may bind. Following binding, a neurotoxin component of the conjugate, which is capable of inhibition of cellular secretion, passes into the cytosol of the target cell by cellular internalisation mechanisms. Thereafter, inhibition of secretion from the target cell is effected.
A method of inhibiting secretion from a non-neuronal inflammatory cell comprising administering an agent comprising at least first and second domains, wherein the first domain cleaves one or more proteins essential to exocytosis and the second domain translocates the first domain into the inflammatory cell.
An agent for inhibiting secretion from a non-neuronal inflammatory cell, comprising at least first, second and third domains, wherein the first domain cleaves one or more proteins essential to exocytosis, the second domain translocates the first domain into the cell and the third domain binds to said non-neuronal inflammatory cell.
An agent for use in gene therapy, comprising a nucleic acid sequence encoding a first domain which cleaves one or more proteins essential to exocytosis, and a second domain associated with the nucleic acid sequence which, following administration to a patient, translocates the nucleic acid sequence into a non-neuronal inflammatory target cell and, when in said non-neuronal inflammatory target cell, expression of the nucleic acid sequence is effected therein.
A method of treating a disease caused, exacerbated or maintained by secretion from a non-neuronal inflammatory cell, said method comprising administering to a patient a polypeptide that cleaves one or more proteins essential to exocytosis, or a nucleic acid encoding said polypeptide, to a patient.
Dependencies are inferred from the claim text.