Clostridial toxin derivatives able to modify peripheral sensory afferent functions

A non-cytotoxic agent that binds to a primary sensory afferent neuron, which comprises:

• 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 neuron, and is capable of functionally interacting with a binding site causing a physical association between the agent and the surface of a primary sensory afferent neuron;
• and the heavy chain (H-chain) of the clostridial neurotoxin is removed or io modified by chemical derivatisation, mutation or proteolysis to reduce or remove 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 that introduces the L-chain or fragment thereof into the cytosol of a primary sensory afferent neuron, thereby inhibiting the transmission of signals between a primary sensory afferent neuron and a projection neuron by controlling the release of at least one neurotransmitter or neuromodulator from the primary sensory afferent neuron.