A new wrinkle on pain relief: re-engineering clostridial neurotoxins for analgesics

Botulinum neurotoxins are used to treat of a range of chronic neuromuscular conditions and, increasingly, conditions involving non-neuromuscular transmission, both cholinergic and non-cholinergic, including chronic pain. However, their clinical use is limited by the potential for adverse effects related to the neuromuscular activity, which results from the selectivity of the toxin for the neuromuscular junction. The elucidation of the structure of the botulinum toxin molecule and its relationship to neurotoxin function has enabled the design of novel molecules incorporating selected aspects of toxin function. This review considers the suitability of engineered neurotoxins as the basis for novel therapeutic proteins and the opportunity of developing analgesics based on these neurotoxins.