People bitten by Alpine vipers are usually treated with
antivenom antisera to prevent the noxious consequences caused by the injected
venom. However, this treatment suffers from a number of drawbacks and additional
therapies are necessary. The
venoms of Vipera ammodytes and of Vipera aspis are neurotoxic and cause muscle
paralysis by inducing neurodegeneration of motor axon terminals because they contain a presynaptic acting
sPLA2 neurotoxin. We have recently found that any type of damage to motor axons is followed by the expression and activation of the intercellular signaling axis consisting of the
CXCR4 receptor present on the membrane of the axon stump and of its
ligand, the
chemokine CXCL12 released by activated terminal Schwann cells. We show here that also V. ammodytes and V. aspis
venoms cause the expression of the CXCL12-CXCR4 axis. We also show that a small molecule agonist of CXCR4, dubbed
NUCC-390, induces a rapid regeneration of the motor axon terminal with functional recovery of the neuromuscular junction. These findings qualify
NUCC-390 as a promising novel
therapeutics capable of improving the recovery from the
paralysis caused by the
snakebite of the two neurotoxic Alpine vipers.