| abstract |
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. |