A conjugate composed of nerve growth factor coupled to a non-toxic derivative of Clostridium botulinum neurotoxin type A can inhibit neurotransmitterrelease in vitro

Nerve growth factor (NGF) receptor binding, internalisation and transportat ion of NGF has been identified as a potential route of delivery for other m olecules. A derivative of Clostridium botulinum neurotoxin type A (LHN) tha t retains catalytic activity but has significantly reduced cell-binding cap ability has been prepared and chemically coupled to NGF, Intact clostridial neurotoxins potently inhibit neurotransmitter release at the neuromuscular junction by proteolysis of specific components of the vesicle docking/fusi on complex. Here we report that the NGF-LHN/A conjugate, when applied to PC 12 cells, significantly inhibited neurotransmitter release and cleaved the type A toxin substrate. This work represents the successful use of NGF as a targeting moiety for the delivery of a neurotoxin fragment.