Using imaging of the neuromuscular junction and electrophysiological analysis, we found that NUCC-390 administration after injection of either the purified neuroparalytic Taipoxin or the whole Taipan venom, significantly accelerates the recovery from paralysis. Here, we have tested its efficacy in a murine model of neuroparalytic envenoming by a Papuan Taipan ( Oxyuranus scutellatus) where a degeneration of the motor axon terminals caused by the presynaptic PLA2 toxin Taipoxin, contained in the venom, occurs. NUCC-390 is an agonist of CXCR4 acting similarly to CXCL12α. This intercellular signaling axis promotes axonal growth and functional recovery from paralysis. These syndromes are characterized by the activation of a pro-regenerative molecular axis, consisting of the CXCR4 receptor expressed at the damaged site in neuronal axons and by the release of its ligand CXCL12α, produced by surrounding Schwann cells. We recently showed that the drug dubbed NUCC-390 shortens the time of recovery from the neuroparalysis caused by traumatic or toxic degeneration of peripheral motor neurons.
There is consensus that additional, not expensive, treatments that can be delivered even long after the snake bite are needed. Hospitalization and use of animal-derived antivenom are the primary therapeutic supports currently available. Envenomation by snakes is a major neglected human disease.
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