ACTH 4-9 analog (Org 2766) improves qualitative and quantitative aspects of motor nerve regeneration

ACTH 1-39 and many of its fragments enhance regeneration of rat peripheral nerve and improve motor unit reorganization. The analog of ACTH 4-9 (Org 2766), with longer-lasting activity and greater biological potency for many parameters, was evaluated for its restorative powers on neuromuscular function following denervation. Org 2766 (10 micrograms/kg/48 hr IP) was administered to rats starting 3 hr after crush denervation of the extensor digitorum longus (EDL) muscle. Contractile strength, motor unit performance under low, optimum and high frequency stimulation, and number and size distribution of motor units of the EDL stimulated through the regenerating peroneal nerve were compared to saline-treated controls. Muscles of parallel animal groups were stimulated directly in vitro. Contractile strength and motor unit performance during high frequency stimulation were significantly improved by Org 2766 treatment at both 7 and 11 days after crush denervation. Org 2766 improves motor unit reformation both qualitatively (more small motor units that are highly resistant to fatigue) and quantitatively (stronger motor units). This peptide does not affect muscle contractile components. Prolonged treatment (21 days) with Org 2766 has a negative effect on motor unit performance, indicating that it exerts its favorable effects early in regeneration and exposure to this peptide should be limited to this period.