Novel Drug Therapy Improved Nerve Regeneration and Function

Background: Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is particularly important when injuries require regeneration over long distances and/or over long time periods. In addition, neurotmesis caused by nerve root avulsion may lead to a progressive loss of axotomized motoneurons (MNs) which sometimes avert warranty for surgical nerve repair. Using a bottom-up experimental approach using rat models of peripheral nerve injuries and sophisticate molecular biology and computational tools we ended up with a selected combination of FDA-approved drugs repurposed for its unexpected use in traumatology. In previous studies, using experimental models of nerve root avulsion, we validated that the drug combination (C1) exerted neuroprotection of almost 60% of spinal motoneurons (MNs) and exhibited anti-inflammatory properties reducing glial reactivity. Currently, we aim to verify the regenerative potential of C1. Methods: We use a model of crush injury in rat (Sprague Dawley) sciatic nerve. To asses functional recovery of denervated muscles, the compound muscle action potentials (CMAP) evoked in response to sciatic nerve stimulation were recorded in gastrocnemius and plantar muscles during the follow up. The recovery of locomotion function was assessed by the walking track analysis. At end point, we analysed neuromuscular junction’s reinnervation by plantar muscle immunohistochemistry. Results: We are now presenting that in a crush model of the sciatic nerve, the animals treated with oral administrated C1 presented acceleration in nerve regeneration analysed by electrophysiological recordings. Treated rats presented around 40 and 60% of increased amplitude of the CMAP of the gastrocnemius and plantar muscles, respectively compared with vehicle group after 35 days post-injury. Consequently, C1 treated rats showed an improved sciatic nerve functional index of 50% respect to controls. Besides, the number of reinnervated end-plates at the plantar muscle was 20% higher in C1 treated rats than in controls. Finally, walking track assessment revealed that locomotor function was better achieved after the treatment with C1. Conclusion: Overall, we set up and validated a new platform for therapy discovery to treat nervous system traumatic injuries.