Envenomation by snakes is a major neglected human disease. Hospitalization and use of animal-derived
antivenom are the primary therapeutic supports currently available. There is consensus that additional, not expensive, treatments that can be delivered even long after the
snake bite are needed. 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. 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. This intercellular signaling axis promotes axonal growth and functional recovery from
paralysis.
NUCC-390 is an agonist of CXCR4 acting similarly to CXCL12α. 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. 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. These results indicate that
NUCC-390, which is non-toxic in mice, should be considered for trials in humans to test its efficacy in accelerating the recovery from the peripheral neuroparalysis induced by Taipans.
NUCC-390 should be tested as well in the envenomation by other snakes that cause neuroparalytic syndromes in humans.
NUCC-390 could become an additional treatment, common to many
snake envenomings, that can be delivered after the
bite to reduce death by respiratory deficits and to shorten and improve functional recovery.