Patent ID: 6395513
Filing Date: 2002-05-28
Classification: A61K,A61P,C07K,Y10S

Abstract:
A method for preparing an agent in the form of a fusion protein, which agent binds to a peripheral sensory afferent,the agent comprising a Targeting Moiety (TM) coupled to a modified clostridial neurotoxin in which the TM comprises a ligand to a cell-surface binding site present on a primary sensory afferent and is capable of functionally interacting with the binding site causing a physical association between the agent and the surface of the primary sensory afferent, wherein the heavy chain (H-chain) of the clostridial neurotoxin is removed or modified to remove or reduce its native binding affinity for motor neurons, and the light chain (L-chain) of the clostridial neurotoxin or a fragment thereof retains a protease activity specific for components of the neurosecretory machinery, the TM and the modified H-chain, if present, forming a molecule which introduces the L-chain or fragment thereof into the cytosol of a primary sensory afferent, thereby inhibiting the transmission of signals between a primary sensory afferent and a projection neuron by controlling the release of at least one neurotransmitter or neuromodulator from the primary sensory afferent; said method comprising expressing in a host organism a genetic construct which codes for the agent.