Botulinum neurotoxin serotype D is poorly effective in humans: an in vivo electrophysiological study.

OBJECTIVE

Botulinum neurotoxins act on nerve endings and block neurotransmitter release. Their potency is due to their enzymatic activity and high affinity binding to neurons. Botulinum toxin type A is used in the treatment of human diseases characterized by hyperactivity of peripheral cholinergic nerve terminals, but some patients are or become resistant to it. This can be overcome by using other botulinum toxins, and studies have been performed with different toxin serotypes. Botulinum neurotoxin type D has never been tested in humans in vivo, and, therefore, we investigated the action of this toxin in mouse and human muscles.

METHODS

Botulinum toxin type D potency was determined on mouse hemidiaphragm and on rat neuronal cultures. From these experiments, doses to be injected in human volunteers were decided. The compound muscle action potential of toxin-injected Extensor Digitorum Brevis muscle was measured at different times points after injection in human volunteers.

RESULTS

Botulinum toxin type D is poorly effective in inducing human skeletal muscle paralysis.

CONCLUSIONS

Botulinum toxin type D is very potent in mice and almost ineffective in humans in vivo.

SIGNIFICANCE: The results shed new light on the mechanism of toxin type D binding to the neuronal surface receptors.